SHORT INTERFERING NUCLEIC ACID (siNA) MOLECULES AND USES THEREOF FOR CORONAVIRUS DISEASES

ABSTRACT

The present invention is in the field of pharmaceutical compounds and preparations and method of their use in the treatment of disease. Described are short interfering nucleic acid (siNA) molecules comprising modified nucleotides, compositions containing the same, and uses thereof for treating or preventing coronavirus infections. In particular, the present invention is in the field of siNA molecules effective against a broad spectrum of coronaviruses, and especially the β-coronaviruses, including SARS-CoV-2, the causative agent of COVID-19.

CROSS-REFERENCE STATEMENT

This application claims priority to U.S. Provisional Application No.63/008,273, filed Apr. 10, 2020, the disclosure of which is herebyincorporated by reference in its entirety.

FIELD OF THE INVENTION

The present invention is in the field of pharmaceutical compounds andpreparations and method of their use in the treatment of disease.Described are short interfering nucleic acid (siNA) molecules comprisingmodified nucleotides, compositions containing the same, and uses thereoffor treating or preventing coronavirus infections. In particular, thepresent invention is in the field of siNA molecules effective against abroad spectrum of coronaviruses, and especially the β-coronaviruses,including SARS-CoV-2, the causative agent of COVID-19.

BACKGROUND

The following discussion is merely provided to aid the reader inunderstanding the disclosure and is not admitted to describe orconstitute prior art thereto.

Coronavirus disease 2019 (COVID-19) (also referred to as novelcoronavirus pneumonia or 2019-nCoV acute respiratory disease) is aninfectious disease caused by the virus severe respiratory syndromecoronavirus 2 (SARS-CoV-2) (also referred to as novel coronavirus 2019,or 2019-nCoV). The disease was first identified in December 2019 andspread globally, causing a pandemic. Symptoms of COVID-19 include fever,cough, shortness of breath, fatigue, headache, loss of smell, nasalcongestion, sore throat, coughing up sputum, pain in muscles or joints,chills, nausea, vomiting, and diarrhea. In severe cases, symptoms caninclude difficulty waking, confusion, blueish face or lips, coughing upblood, decreased white blood cell count, and kidney failure.Complications can include pneumonia, viral sepsis, acute respiratorydistress syndrome, and kidney failure.

COVID-19 is especially threatening to public health. The virus is highlycontagious, and studies currently indicate that it can be spread byasymptomatic carriers or by those who are pre-symptomatic. Likewise, theearly stage of the disease is slow-progressing enough that carriers donot often realize they are infected, leading them to expose numerousothers to the virus. The combination of COVID-19's ease of transmission,its high rate of hospitalization of victims, and its death rate make thevirus a substantial public health risk, especially for countries withouta healthcare system equipped to provide supportive care topandemic-level numbers of patients. There is not yet a vaccine orspecific antiviral treatment for COVID-19 and accordingly, there is apressing need for treatments or cures.

SARS-CoV-2 is not the only coronavirus that causes disease. It is aβ-coronavirus, a genus of coronaviruses that includes other humanpathogens, including SARS-CoV (the causative agent of SARS), MERS-CoV(the causative agent of MERS), and HCoV-OC43 (a causative agent of thecommon cold). The infectivity of these viruses, and the severity of thediseases they cause, varies widely. B-coronaviruses can also manifest aszoonotic infections, spread to and from humans and animals.Additionally, non-human species such as camels, bats, tigers, non-humanprimates, and rabbits can be susceptible to β-coronaviruses.Accordingly, there is a pressing need for treatments or cures tomultiple coronaviruses.

RNA interference (RNAi) is a biological response to double-stranded RNAthat mediates resistance to both endogenous parasitic and exogenouspathogenic nucleic acids, and regulates the expression of protein-codinggenes. The short interfering nucleic acids (siNA), such as siRNA, havebeen developed for RNAi therapy to treat a variety of diseases. Forinstance, RNAi therapy has been proposed for the treatment of metabolicdiseases, neurodegenerative diseases, cancer, and pathogenic infections(See e.g., Rondindone, Biotechniques, 2018, 40(4S),doi.org/10.2144/000112163, Boudreau and Davidson, Curr Top Dev Biol,2006, 75:73-92, Chalbatani et al., Int J Nanomedicine, 2019,14:3111-3128, Arbuthnot, Drug News Perspect, 2010, 23(6):341-50, andChernikov et. al., Front. Pharmacol., 2019,doi.org/10.3389/fphar.2019.00444, each of which are incorporated byreference in their entirety).

The present disclosure provides siNA molecules useful againstcoronaviruses, and especially SARS-CoV-2, the causative agent ofCOVID-19. Accordingly, the present disclosure fulfills the need in theart for compounds that can be safely and effectively treat or preventcoronavirus infections in humans.

SUMMARY OF THE INVENTION

Disclosed herein are short interfering nucleic acid (siNA) molecules,which can be used to treat and/or prevent viral disease and infections,such as diseases (e.g., COVID-19) or infections caused by coronaviruslike SARS-CoV-2. In some embodiments, the siNA can be a double-strandedsiNA (ds-siNA).

In one aspect, the present disclosure provides siNA that comprise (a) asense strand comprising a first nucleotide sequence, wherein the firstnucleotide sequence is 15 to 30 nucleotides in length and comprises anucleotide sequence that is at least about 60%, 65%, 70%, 75%, 80%, 85%,90%, 95%, or 100% identical to an RNA corresponding to of any one of SEQID NOs: 1-1203 and 2411-3392; and (b) an antisense strand comprising asecond nucleotide sequence, wherein the second nucleotide sequence is 15to 30 nucleotides in length and comprises a nucleotide sequence that isat least about 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, or 100%complementary to the first nucleotide sequence.

In another aspect, the present disclosure provides siNA that comprise asense strand comprises (a) a first nucleotide sequence, wherein thefirst nucleotide sequence is identical to an RNA corresponding to 15 to30 nucleotides within positions 190-216, 233-279, 288-324, 455-477,626-651, 704-723, 3352-3378, 5384-5403, 6406-6483, 7532-7551, 9588-9606,10484-10509, 11609-11630, 11834-11853, 12023-12045, 12212-12234,12401-12420, 12839-12867, 12885-12924, 12966-12990, 13151-13176,13363-13386, 13388-13416, 13458-13416, 13458-13520, 13762-13790,14290-14312, 14404-14429, 14500-14531, 14623-14642, 14650-14687,14698-14717, 14722-14748, 14750-14777, 14821-14846, 14854-14873,14875-14903, 14962-14990, 14992-15020, 15055-15140, 15172-15200,15310-15332, 15346-15367, 15496-15518, 15622-15644, 15838-15869,15886-15905, 15985-16010, 16057-16079, 16186-16205, 16430-16448,16822-16865, 16954-16976, 17008-17042, 17080-17111, 17137-17156,17269-17289, 17530-17549, 17563-17582, 17680-17699, 17746-17765,17857-17876, 17956-17975, 18100-18122, 18196-18218, 19618-19639,19783-19802, 19831-19850, 20107-20130, 20776-20795, 21502-21524,24302-24325, 24446-24465, 24620-24651, 24662-24684, 25034-25057,25104-25128, 25364-25387, 25502-25530, 26191-26227, 26232-26267,26269-26330, 26332-26394, 26450-26481, 26574-26600, 27003-27064,27093-27111, 27183-27212, 27382-27407, 27511-27533, 27771-27818,28270-28296, 28397-28434, 28513-28546, 28673-28692, 28706-28726,28744-28794, 28799-28827, 28946-28972, 28976-29034, 29144-29172,29174-29196, 29228-29259, 29285-29305, 29342-29394, 29444-29463,29543-29566, 29598-29630, 29652-29687, 29689-29731, 29733-29757, or29770-29828 of SEQ ID NO: 2407 and (b) an antisense strand.

In another aspect, the present disclosure provides siNA that comprise anantisense strand comprising (a) a second nucleotide sequence, whereinthe second nucleotide sequence is complementary to an RNA correspondingto 15 to 30 nucleotides within positions 190-216, 233-279, 288-324,455-477, 626-651, 704-723, 3352-3378, 5384-5403, 6406-6483, 7532-7551,9588-9606, 10484-10509, 11609-11630, 11834-11853, 12023-12045,12212-12234, 12401-12420, 12839-12867, 12885-12924, 12966-12990,13151-13176, 13363-13386, 13388-13416, 13458-13416, 13458-13520,13762-13790, 14290-14312, 14404-14429, 14500-14531, 14623-14642,14650-14687, 14698-14717, 14722-14748, 14750-14777, 14821-14846,14854-14873, 14875-14903, 14962-14990, 14992-15020, 15055-15140,15172-15200, 15310-15332, 15346-15367, 15496-15518, 15622-15644,15838-15869, 15886-15905, 15985-16010, 16057-16079, 16186-16205,16430-16448, 16822-16865, 16954-16976, 17008-17042, 17080-17111,17137-17156, 17269-17289, 17530-17549, 17563-17582, 17680-17699,17746-17765, 17857-17876, 17956-17975, 18100-18122, 18196-18218,19618-19639, 19783-19802, 19831-19850, 20107-20130, 20776-20795,21502-21524, 24302-24325, 24446-24465, 24620-24651, 24662-24684,25034-25057, 25104-25128, 25364-25387, 25502-25530, 26191-26227,26232-26267, 26269-26330, 26332-26394, 26450-26481, 26574-26600,27003-27064, 27093-27111, 27183-27212, 27382-27407, 27511-27533,27771-27818, 28270-28296, 28397-28434, 28513-28546, 28673-28692,28706-28726, 28744-28794, 28799-28827, 28946-28972, 28976-29034,29144-29172, 29174-29196, 29228-29259, 29285-29305, 29342-29394,29444-29463, 29543-29566, 29598-29630, 29652-29687, 29689-29731,29733-29757, or 29770-29828 of SEQ ID NO: 2407 and (b) a sense strand.

In another aspect, the present disclosure provides siNA that comprise(a) a sense strand comprising a nucleotide sequence identical to an RNAcorresponding to any one of SEQ ID NOs: 1-1203 and 2411-3392 and (b) anantisense strand.

In another aspect, the present disclosure provides siNA that comprise(a) an antisense strand comprising a nucleotide sequence identical to anRNA corresponding to any one of SEQ ID NOs: 1204-2406 and 3393-4374 and(b) a sense strand.

In some embodiments, the sense strand can comprise 15 or more modifiednucleotides independently selected from a 2′-O-methyl nucleotide and a2′-fluoro nucleotide, wherein at least one modified nucleotide is a2′-O-methyl nucleotide and the nucleotide at position 3, 5, 7, 8, 9, 10,11, 12, 14, 17, and/or 19 from the 5′ end is a 2′-fluoro nucleotide; andthe antisense strand can comprise 15 or more modified nucleotidesindependently selected from a 2′-O-methyl nucleotide and a 2′-fluoronucleotide, wherein at least one modified nucleotide is a 2′-O-methylnucleotide and at least one modified nucleotide is a 2′-fluoronucleotide.

In some embodiments, the sense strand can comprise 15 or more modifiednucleotides independently selected from a 2′-O-methyl nucleotide and a2′-fluoro nucleotide, wherein at least one modified nucleotide is a2′-O-methyl nucleotide and at least one modified nucleotide is a2′-fluoro nucleotide; and the antisense strand can comprise 15 or moremodified nucleotides independently selected from a 2′-O-methylnucleotide and a 2′-fluoro nucleotide, wherein at least one modifiednucleotide is a 2′-O-methyl nucleotide and the nucleotide at position 2,5, 6, 8, 10, 14, 16, 17, and/or 18 from the 5′ end is a 2′-fluoronucleotide.

In some embodiments, the sense strand can comprise 16, 17, 18, 19, 20,21, 22, 23, or more modified nucleotides independently selected from a2′-O-methyl nucleotide and a 2′-fluoro nucleotide. In some embodiments,70%, 75%, 80%, 85%, 90%, 95% or 100% of the nucleotides in the sensestrand can be modified nucleotides independently selected from a2′-O-methyl nucleotide and a 2′-fluoro nucleotide.

In some embodiments, (i) at least 2, 3, 4, 5, or 6 modified nucleotidesof the sense strand are 2′-fluoro nucleotides; (ii) no more than 10, 9,8, 7, 6, 5, 4, 3, or 2 modified nucleotides of the sense strand are2′-fluoro nucleotides; (iii) at least 10, 11, 12, 13, 14, 15, 16, 17,18, 19, 20, 21, or 22 modified nucleotides of the sense strand sequenceare 2′-O-methyl nucleotides; and/or (iv) no more than 25, 24, 23, 22,21, 20, 19, 18, 17, 16, 15, 14, 13, 12, 11, 10, 9, 8, 7, 6, 5, 4, 3, or2 modified nucleotides of the sense strand are 2′-O-methyl nucleotides.

In some embodiments, the antisense strand can comprise 16, 17, 18, 19,20, 21, 22, 23, or more modified nucleotides independently selected froma 2′-O-methyl nucleotide and a 2′-fluoro nucleotide. In someembodiments, 70%, 75%, 80%, 85%, 90%, 95% or 100% of the nucleotides inthe antisense strand are modified nucleotides independently selectedfrom a 2′-O-methyl nucleotide and a 2′-fluoro nucleotide.

In some embodiments, (i) at least 2, 3, 4, 5, or 6 modified nucleotidesof the antisense strand are 2′-fluoro nucleotides; (ii) no more than 10,9, 8, 7, 6, 5, 4, 3, or 2 modified nucleotides of the antisense strandare 2′-fluoro nucleotides; (iii) at least 10, 11, 12, 13, 14, 15, 16,17, 18, 19, 20, 21, or 22 modified nucleotides of the antisense strandsequence are 2′-O-methyl nucleotides; and/or (iv) no more than 25, 24,23, 22, 21, 20, 19, 18, 17, 16, 15, 14, 13, 12, 11, 10, 9, 8, 7, 6, 5,4, 3, or 2 modified nucleotides of the antisense strand are 2′-O-methylnucleotides.

In some embodiments, the sense strand and/or the antisense strand cancomprise one or more phosphorothioate internucleoside linkage(s). Insome embodiments, the siNA can further comprise a phosphorylationblocker and/or a 5′-stabilized end cap.

In some embodiments, the sense strand can further comprise a TT sequenceadjacent to the first nucleotide sequence.

In some embodiments, at least one end of the siNA can be a blunt end. Insome embodiments, at least one end of the siNA can comprise an overhang,wherein the overhang comprises at least one nucleotide. In someembodiments, both ends of the siNA can comprise an overhang, wherein theoverhang comprises at least one nucleotide.

In some embodiments, the sense strand can further comprise at least 1,2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15 or more phosphorothioateinternucleotide linkages. In some embodiments, the antisense strand canfurther comprise at least 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14,15 or more phosphorothioate internucleotide linkages.

In some embodiments, the sense strand and/or the antisense strand cancomprise one or more modified nucleotides. In some embodiments, themodified nucleotides are independently selected from 2′-O-methylnucleotides and 2′-fluoro nucleotides. In some embodiments, at least one2′-fluoro nucleotide or 2′-O-methyl nucleotide is a 2′-fluoro or2′-O-methyl nucleotide mimic of Formula (V):

wherein R¹ is a nucleobase, aryl, heteroaryl, or H, Q¹ and Q² areindependently S or O, R⁵ is —OCD₃, —F, or —OCH₃, and R⁶ and R⁷ areindependently H or D.

In some embodiments, the sense strand and/or antisense strand comprisesat least one modified nucleotide selected from

where R is H or alkyl (or AmNA(N-Me)) when R is alkyl);

wherein B is a nucleobase.

In some embodiments, the siNA can further comprise a phosphorylationblocker and/or a 5′-stabilized end cap. In some embodiments, thephosphorylation blocker has the structure of Formula (IV):

wherein R¹ is a nucleobase, R⁴ is —O—R³⁰ or —NR³¹R³², R³⁰ is C₁-C₈substituted or unsubstituted alkyl; andR³¹ and R³² together with the nitrogen to which they are attached form asubstituted or unsubstituted heterocyclic ring. In some embodiments, R⁴is —OCH₃ or —N(CH₂CH₂)₂O. In some embodiments, the phosphorylationblocker is attached to the 5′ end of the sense strand. In someembodiments, the phosphorylation blocker is attached to the 5′ end ofthe sense strand via one or more linkers independently selected from aphosphodiester linker, phosphorothioate linker, and phosphorodithioatelinker.

In some embodiments, the 5′-stabilized end cap is a 5′ vinylphosphonate.In some embodiments, the 5′ vinylphosphonate is selected from a5′-(E)-vinyl phosphonate or 5′-(Z)-vinyl phosphonate. In someembodiments, the 5′-vinylphosphonate is a deuterated vinyl phosphonate.In some embodiments, the deuterated vinylphosphonate is amono-deuterated vinylphosphonate or a di-deuterated vinylphosphonate

In some embodiments, the 5′-stabilized end cap has the structure ofFormula (Ia):

wherein R¹ is a nucleobase, aryl, heteroaryl, or H; R² is

—CH═CD-Z, —CD=CH—Z, —CD=CD-Z, —(CR²¹R²²)_(n)—Z or —(C₂-C₆ alkenylene)-Zand R²⁰ is hydrogen, or R² and R²⁰ together form a 3- to 7-memberedcarbocyclic ring substituted with —(CR²¹R²²)_(n)—Z or —(C₂-C₆alkenylene)-Z; n is 1, 2, 3, or 4;Z is —ONR²³R²⁴, —OP(O)OH(CH₂)_(m)CO₂R²³, —OP(S)OH(CH₂)_(m)CO₂R²³,—P(O)(OH)₂, —P(O)(OH)(OCH₃), —P(O)(OH)(OCD₃), —SO₂(CH₂)_(m)P(O)(OH)₂,—SO₂NR²³R²⁵, —NR²³R²⁴, or —NR²³SO₂R²⁵; R²¹ and R²² either areindependently hydrogen or C₁-C₆ alkyl, or R²¹ and R²² together form anoxo group; R²³ is hydrogen or C₁-C₆ alkyl, R²⁴ is —SO₂R²⁵ or —C(O)R²⁵,or R²³ and R²⁴ together with the nitrogen to which they are attachedform a substituted or unsubstituted heterocyclic ring; R²⁵ is C₁-C₆alkyl; and m is 1, 2, 3, or 4. In some embodiments, R¹ is an aryl. Insome embodiments, the aryl is a phenyl.

In some embodiments, the 5′-stabilized end cap has the structure ofFormula (Ib):

whereinR¹ is a nucleobase, aryl, heteroaryl, or H,

R² is

—CH═CD-Z, —CD=CH—Z, —CD=CD-Z, —(CR²¹R²²)_(n)—Z, or —(C₂-C₆ alkenylene)-Zand R²⁰ is hydrogen; orR² and R²⁰ together form a 3- to 7-membered carbocyclic ring substitutedwith —(CR²¹R²²)_(n)—Z or —(C₂-C₆ alkenylene)-Z;n is 1, 2, 3, or 4;Z is —ONR²³R²⁴, —OP(O)OH(CH₂)_(m)CO₂R²³, —OP(S)OH(CH₂)_(m)CO₂R²³,—P(O)(OH)₂, —P(O)(OH)(OCH₃), —P(O)(OH)(OCD₃), —SO₂(CH₂)_(m)P(O)(OH)₂,—SO₂NR²³R²⁵, —NR²³R²⁴,R²¹ and R²² are independently hydrogen or C₁-C₆ alkyl; R²¹ and R²²together form an oxo group;R²³ is hydrogen or C₁-C₆ alkyl;R²⁴ is —SO₂R²⁵ or —C(O)R²⁵; orR²³ and R²⁴ together with the nitrogen to which they are attached form asubstituted or unsubstituted heterocyclic ring;R²⁵ is C₁-C₆ alkyl; andm is 1, 2, 3, or 4.

In some embodiments, the 5′-stabilized end cap is selected from thegroup consisting of Formula (1) to Formula (15), Formula (9X) to Formula(12X), and Formula (9Y) to Formula (12Y):

wherein R¹ is a nucleobase, aryl, heteroaryl, or H.

In some embodiments, the 5′-stabilized end cap is selected from thegroup consisting of Formulas (1A)-(15A), Formulas (9B)-(12B), Formulas(9AX)-(12AX), Formulas (9AY)-(12AY), Formulas (9BX)-(12BX), and Formulas(9BY)-(12BY):

In some embodiments, the 5′-stabilized end cap can be attached to the 5′end of the antisense strand. In some embodiments, the 5′-stabilized endcap can be attached to the 5′ end of the antisense strand via one ormore linkers independently selected from a phosphodiester linker,phosphorothioate linker, phosphoramidite (HEG) linker, triethyleneglycol (TEG) linker, or phosphorodithioate linker.

In some embodiments, the sense strand consists of 21 nucleotides. Insome embodiments, 2′-O-methyl nucleotides are at positions 18-21 fromthe 5′ end of the sense strand.

In some embodiments, the antisense strand consists of 23 nucleotides. Insome embodiments, 2′-O-methyl nucleotides are at positions 18-23 fromthe 5′ end of the antisense strand.

In another aspect, the present disclosure provides, a siNA selected fromds-siNA-005; ds-siNA-006; ds-siNA-007; ds-siNA-008; ds-siNA-009;ds-siNA-010; ds-siNA-011; ds-siNA-012; ds-siNA-013; ds-siNA-014;ds-siNA-015; ds-siNA-016; ds-siNA-017; ds-siNA-018; ds-siNA-019;ds-siNA-020; ds-siNA-021; ds-siNA-022; ds-siNA-023; ds-siNA-024;ds-siNA-025; ds-siNA-026; ds-siNA-027; ds-siNA-028; ds-siNA-029;ds-siNA-030; ds-siNA-031; ds-siNA-032; ds-siNA-033; ds-siNA-034;ds-siNA-035; ds-siNA-036; ds-siNA-037; ds-siNA-038; ds-siNA-039;ds-siNA-040; ds-siNA-041; ds-siNA-042; ds-siNA-043; ds-siNA-044;ds-siNA-045; ds-siNA-046; ds-siNA-047; ds-siNA-048; ds-siNA-049;ds-siNA-050; ds-siNA-051; ds-siNA-052; ds-siNA-053; ds-siNA-054;ds-siNA-055; ds-siNA-056; ds-siNA-057; ds-siNA-058; ds-siNA-059;ds-siNA-060; ds-siNA-061; ds-siNA-062; ds-siNA-063; ds-siNA-064;ds-siNA-065; ds-siNA-066; ds-siNA-067; ds-siNA-068; ds-siNA-069;ds-siNA-070; ds-siNA-071; ds-siNA-072; ds-siNA-073; ds-siNA-074;ds-siNA-075; ds-siNA-076; ds-siNA-077; ds-siNA-078; ds-siNA-079;ds-siNA-080; ds-siNA-081; ds-siNA-082; ds-siNA-083; ds-siNA-084;ds-siNA-085; ds-siNA-086; ds-siNA-087; ds-siNA-088; ds-siNA-089;ds-siNA-090; ds-siNA-091; ds-siNA-092; ds-siNA-093; ds-siNA-094;ds-siNA-095; ds-siNA-096; ds-siNA-097; ds-siNA-098; ds-siNA-099;ds-siNA-100; ds-siNA-101; ds-siNA-102; ds-siNA-103; ds-siNA-104;ds-siNA-105; ds-siNA-106; ds-siNA-107; ds-siNA-108; ds-siNA-109;ds-siNA-110; ds-siNA-111; ds-siNA-112; ds-siNA-113; ds-siNA-114;ds-siNA-115; ds-siNA-116; ds-siNA-117; ds-siNA-118; ds-siNA-119;ds-siNA-120; ds-siNA-121; ds-siNA-122; ds-siNA-123; ds-siNA-124;ds-siNA-125; ds-siNA-126; ds-siNA-127; ds-siNA-128; ds-siNA-129;ds-siNA-130; ds-siNA-131; ds-siNA-132; ds-siNA-133; ds-siNA-134;ds-siNA-135; ds-siNA-136; ds-siNA-137; ds-siNA-138; ds-siNA-139;ds-siNA-140; ds-siNA-141; ds-siNA-142; ds-siNA-143; ds-siNA-144;ds-siNA-145; ds-siNA-146; ds-siNA-147; ds-siNA-148; ds-siNA-149;ds-siNA-150; ds-siNA-151; ds-siNA-152; ds-siNA-153; ds-siNA-154;ds-siNA-155; ds-siNA-156; ds-siNA-157; ds-siNA-158; ds-siNA-159;ds-siNA-160; ds-siNA-161; ds-siNA-162; ds-siNA-163; ds-siNA-164;ds-siNA-165; ds-siNA-166; ds-siNA-167; ds-siNA-168; ds-siNA-169;ds-siNA-170; ds-siNA-171; ds-siNA-172; ds-siNA-173; ds-siNA-174;ds-siNA-175; ds-siNA-176; ds-siNA-177; ds-siNA-178; ds-siNA-179;ds-siNA-180; ds-siNA-181; ds-siNA-182; ds-siNA-183; ds-siNA-184;ds-siNA-185; ds-siNA-186; ds-siNA-187; ds-siNA-188; ds-siNA-189;ds-siNA-190; ds-siNA-191; ds-siNA-192; ds-siNA-193; ds-siNA-194;ds-siNA-195; ds-siNA-196; ds-siNA-197; ds-siNA-198; ds-siNA-199;ds-siNA-200; ds-siNA-201; ds-siNA-202; ds-siNA-203; ds-siNA-204;ds-siNA-205; ds-siNA-206; ds-siNA-207; ds-siNA-208; ds-siNA-209;ds-siNA-210; ds-siNA-211; ds-siNA-212; ds-siNA-213; ds-siNA-214;ds-siNA-215; ds-siNA-216; ds-siNA-217; ds-siNA-218; ds-siNA-219;ds-siNA-220; ds-siNA-221; and ds-siNA-222.

In some embodiments, the siNA is selected from ds-siNA-196 (sense andantisense respectively comprising SEQ ID NOs: 4578 and 4800),ds-siNA-197 (sense and antisense respectively comprising SEQ ID NOs:4579 and 4801), ds-siNA-198 (sense and antisense respectively comprisingSEQ ID NOs: 4580 and 4802), ds-siNA-199 (sense and antisenserespectively comprising SEQ ID NOs: 4581 and 4803), ds-siNA-217 (senseand antisense respectively comprising SEQ ID NOs: 4599 and 4821),ds-siNA-218 (sense and antisense respectively comprising SEQ ID NOs:4600 and 4822), ds-siNA-219 (sense and antisense respectively comprisingSEQ ID NOs: 4601 and 4823), ds-siNA-220 (sense and antisenserespectively comprising SEQ ID NOs: 4602 and 4824), ds-siNA-221 (senseand antisense respectively comprising SEQ ID NOs: 4603 and 4825), andds-siNA-222 (sense and antisense respectively comprising SEQ ID NOs:4604 and 4826).

In some embodiments, the siNA is selected from ds-siNA-196 (sense andantisense respectively comprising SEQ ID NOs: 4578 and 4800),ds-siNA-197 (sense and antisense respectively comprising SEQ ID NOs:4579 and 4801), ds-siNA-198 (sense and antisense respectively comprisingSEQ ID NOs: 4580 and 4802), and ds-siNA-199 (sense and antisenserespectively comprising SEQ ID NOs: 4581 and 4803).

In some embodiments, the siNA is selected from, ds-siNA-217 (sense andantisense respectively comprising SEQ ID NOs: 4599 and 4821),ds-siNA-218 (sense and antisense respectively comprising SEQ ID NOs:4600 and 4822), ds-siNA-219 (sense and antisense respectively comprisingSEQ ID NOs: 4601 and 4823), ds-siNA-220 (sense and antisenserespectively comprising SEQ ID NOs: 4602 and 4824), ds-siNA-221 (senseand antisense respectively comprising SEQ ID NOs: 4603 and 4825), andds-siNA-222 (sense and antisense respectively comprising SEQ ID NOs:4604 and 4826).

In another aspect, the present disclosure provides pharmaceuticalcompositions comprising at least one siNA according to any one of theembodiments described herein and a pharmaceutically acceptable carrieror diluent.

In some embodiments, the pharmaceutical composition can comprise two ormore siNA according to any of the embodiments described herein.

In another aspect, the present disclosure provides methods for treatinga disease in a subject in need thereof, comprising administering thesubject a pharmaceutical composition according to any of the embodimentsdescribed herein.

In another aspect, the present disclosure provides uses of a ds-siRNAaccording to any of the embodiments described herein in the manufactureof a medicament for treating a disease.

In another aspect, the present disclosure provides methods for treatinga disease in a subject in need thereof, comprising administering thesubject a siNA according to any of the embodiments described herein. Insome embodiments, wherein the disease is a viral disease. In someembodiments, the viral disease is caused by an RNA virus. In someembodiments, the RNA virus is a single-stranded RNA virus (ssRNA virus).In some embodiments, the ssRNA virus is a positive-sense single-strandedRNA virus ((+)ssRNA virus). In some embodiments, the (+)ssRNA virus is acoronavirus. In some embodiments, the coronavirus is a β-coronavirus. Insome embodiments, the β-coronavirus is severe acute respiratory syndromecoronavirus 2 (SARS-CoV-2) (also known by the provisional name 2019novel coronavirus, or 2019-nCoV), human coronavirus OC43 (hCoV-OC43),Middle East respiratory syndrome-related coronavirus (MERS-CoV, alsoknown by the provisional name 2012 novel coronavirus, or 2012-nCoV), orsevere acute respiratory syndrome-related coronavirus (SARS-CoV, alsoknown as SARS-CoV-1). In some embodiments, the β-coronavirus isSARS-CoV-2. In some embodiments, the (3-coronavirus is SARS-CoV. In someembodiments, the β-coronavirus is MERS-CoV. In some embodiments, theβ-coronavirus is hCoV-OC43.

In some embodiments, the disease is a respiratory disease. In someembodiments, the respiratory disease is viral pneumonia. In someembodiments, the respiratory disease is an acute respiratory infection.In some embodiments, the respiratory disease is a cold. In someembodiments, the respiratory disease is severe acute respiratorysyndrome (SARS). In some embodiments, the respiratory disease is MiddleEast respiratory syndrome (MERS). In some embodiments, the disease iscoronavirus disease 2019 (COVID-19). In some embodiments, therespiratory disease causes one or more symptoms selected from coughing,sore throat, runny nose, sneezing, headache, fever, shortness of breath,myalgia, abdominal pain, fatigue, difficulty breathing, persistent chestpain or pressure, difficulty waking, loss of smell and taste, muscle orjoint pain, chills, nausea or vomiting, nasal congestion, diarrhea,haemoptysis, conjunctival congestion, sputum production, chesttightness, and palpitations. In some embodiments, the respiratorydisease can cause complications selected from sinusitis, otitis media,pneumonia, acute respiratory distress syndrome, disseminatedintravascular coagulation, pericarditis, and kidney failure. In someembodiments, the respiratory disease is idiopathic.

In another aspect, the present disclosure provides methods of treating aβ-coronavirus-caused disease in a subject in need thereof, comprisingadministering the subject a siNA comprising a sense strand that is 15 to30 nucleotides in length, wherein the sense strand is at least about60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, or 100% identical to a sequencewithin a region of either two, three, or four of SEQ ID NOs: 2407, 2408,2409, and 2410. In some embodiments, the sense strand is identical to anRNA sequence corresponding to a region of each of SEQ ID NOs: 2407,2408, 2409, and 2410. In some embodiments, the sense strand is selectedfrom the group consisting of sequences corresponding to SEQ ID NOs:1-1203 and 2411-3392.

In another aspect, the present disclosure provides methods of treating aβ-coronavirus-caused disease in a subject in need thereof, comprisingadministering the subject a siNA comprising antisense strand that is 15to 30 nucleotides in length, wherein the antisense strand iscomplementary to a sequence within a region of either two, three, orfour of SEQ ID NOs: 2407, 2408, 2409, and 2410. In some embodiments, thesecond nucleotide sequence is at least about 60%, 65%, 70%, 75%, 80%,85%, 90%, 95%, or 100% complementary to an RNA sequence corresponding toa region of each of SEQ ID NOs: 2407, 2408, 2409, and 2410. In someembodiments, the antisense strand comprises a sequence corresponding toone of SEQ ID NOs: 1204-2406 and 3393-4374.

In another aspect, the present disclosure provides methods of treating aβ-coronavirus-caused disease in a subject in need thereof, comprisingadministering the subject a siNA comprising a sense strand that is 15 to30 nucleotides in length, wherein the sense strand is at least about60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, or 100% identical to a sequencewithin a region of either two, three, or four of the genomes of severeacute respiratory syndrome coronavirus 2 (SARS-CoV-2), human coronavirusOC43 (hCoV-OC43), Middle East respiratory syndrome-related coronavirus(MERS-CoV), and severe acute respiratory syndrome-related coronavirus(SARS-CoV). In some embodiments, the sense strand is identical to asequence within a region of each of the genomes of severe acuterespiratory syndrome coronavirus 2 (SARS-CoV-2), human coronavirus OC43(hCoV-OC43), Middle East respiratory syndrome-related coronavirus(MERS-CoV), and severe acute respiratory syndrome-related coronavirus(SARS-CoV).

In another aspect, the present disclosure provides methods of treating aβ-coronavirus-caused disease in a subject in need thereof, comprisingadministering the subject a siNA comprising an antisense strand that is15 to 30 nucleotides in length, wherein the antisense strand is at leastabout 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, or 100% complementary to asequence within a region of either two, three, or four of the genomes ofsevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2), humancoronavirus OC43 (hCoV-OC43), Middle East respiratory syndrome-relatedcoronavirus (MERS-CoV), and severe acute respiratory syndrome-relatedcoronavirus (SARS-CoV). In some embodiments, the second nucleotidesequence is complementary to a sequence within a region of each of thegenomes of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2),human coronavirus OC43 (hCoV-OC43), Middle East respiratorysyndrome-related coronavirus (MERS-CoV), and severe acute respiratorysyndrome-related coronavirus (SARS-CoV).

A method of treating a β-coronavirus-caused disease in a subject in needthereof, comprising administering the subject a siNA selected fromds-siNA-005; ds-siNA-006; ds-siNA-007; ds-siNA-008; ds-siNA-009;ds-siNA-010; ds-siNA-011; ds-siNA-012; ds-siNA-013; ds-siNA-014;ds-siNA-015; ds-siNA-016; ds-siNA-017; ds-siNA-018; ds-siNA-019;ds-siNA-020; ds-siNA-021; ds-siNA-022; ds-siNA-023; ds-siNA-024;ds-siNA-025; ds-siNA-026; ds-siNA-027; ds-siNA-028; ds-siNA-029;ds-siNA-030; ds-siNA-031; ds-siNA-032; ds-siNA-033; ds-siNA-034;ds-siNA-035; ds-siNA-036; ds-siNA-037; ds-siNA-038; ds-siNA-039;ds-siNA-040; ds-siNA-041; ds-siNA-042; ds-siNA-043; ds-siNA-044;ds-siNA-045; ds-siNA-046; ds-siNA-047; ds-siNA-048; ds-siNA-049;ds-siNA-050; ds-siNA-051; ds-siNA-052; ds-siNA-053; ds-siNA-054;ds-siNA-055; ds-siNA-056; ds-siNA-057; ds-siNA-058; ds-siNA-059;ds-siNA-060; ds-siNA-061; ds-siNA-062; ds-siNA-063; ds-siNA-064;ds-siNA-065; ds-siNA-066; ds-siNA-067; ds-siNA-068; ds-siNA-069;ds-siNA-070; ds-siNA-071; ds-siNA-072; ds-siNA-073; ds-siNA-074;ds-siNA-075; ds-siNA-076; ds-siNA-077; ds-siNA-078; ds-siNA-079;ds-siNA-080; ds-siNA-081; ds-siNA-082; ds-siNA-083; ds-siNA-084;ds-siNA-085; ds-siNA-086; ds-siNA-087; ds-siNA-088; ds-siNA-089;ds-siNA-090; ds-siNA-091; ds-siNA-092; ds-siNA-093; ds-siNA-094;ds-siNA-095; ds-siNA-096; ds-siNA-097; ds-siNA-098; ds-siNA-099;ds-siNA-100; ds-siNA-101; ds-siNA-102; ds-siNA-103; ds-siNA-104;ds-siNA-105; ds-siNA-106; ds-siNA-107; ds-siNA-108; ds-siNA-109;ds-siNA-110; ds-siNA-111; ds-siNA-112; ds-siNA-113; ds-siNA-114;ds-siNA-115; ds-siNA-116; ds-siNA-117; ds-siNA-118; ds-siNA-119;ds-siNA-120; ds-siNA-121; ds-siNA-122; ds-siNA-123; ds-siNA-124;ds-siNA-125; ds-siNA-126; ds-siNA-127; ds-siNA-128; ds-siNA-129;ds-siNA-130; ds-siNA-131; ds-siNA-132; ds-siNA-133; ds-siNA-134;ds-siNA-135; ds-siNA-136; ds-siNA-137; ds-siNA-138; ds-siNA-139;ds-siNA-140; ds-siNA-141; ds-siNA-142; ds-siNA-143; ds-siNA-144;ds-siNA-145; ds-siNA-146; ds-siNA-147; ds-siNA-148; ds-siNA-149;ds-siNA-150; ds-siNA-151; ds-siNA-152; ds-siNA-153; ds-siNA-154;ds-siNA-155; ds-siNA-156; ds-siNA-157; ds-siNA-158; ds-siNA-159;ds-siNA-160; ds-siNA-161; ds-siNA-162; ds-siNA-163; ds-siNA-164;ds-siNA-165; ds-siNA-166; ds-siNA-167; ds-siNA-168; ds-siNA-169;ds-siNA-170; ds-siNA-171; ds-siNA-172; ds-siNA-173; ds-siNA-174;ds-siNA-175; ds-siNA-176; ds-siNA-177; ds-siNA-178; ds-siNA-179;ds-siNA-180; ds-siNA-181; ds-siNA-182; ds-siNA-183; ds-siNA-184;ds-siNA-185; ds-siNA-186; ds-siNA-187; ds-siNA-188; ds-siNA-189;ds-siNA-190; ds-siNA-191; ds-siNA-192; ds-siNA-193; ds-siNA-194;ds-siNA-195; ds-siNA-196; ds-siNA-197; ds-siNA-198; ds-siNA-199;ds-siNA-200; ds-siNA-201; ds-siNA-202; ds-siNA-203; ds-siNA-204;ds-siNA-205; ds-siNA-206; ds-siNA-207; ds-siNA-208; ds-siNA-209;ds-siNA-210; ds-siNA-211; ds-siNA-212; ds-siNA-213; ds-siNA-214;ds-siNA-215; ds-siNA-216; ds-siNA-217; ds-siNA-218; ds-siNA-219;ds-siNA-220; ds-siNA-221; and ds-siNA-222. In some embodiments, the siNAis selected from ds-siNA-196 (sense and antisense respectivelycomprising SEQ ID NOs: 4578 and 4800), ds-siNA-197 (sense and antisenserespectively comprising SEQ ID NOs: 4579 and 4801), ds-siNA-198 (senseand antisense respectively comprising SEQ ID NOs: 4580 and 4802),ds-siNA-199 (sense and antisense respectively comprising SEQ ID NOs:4581 and 4803), ds-siNA-217 (sense and antisense respectively comprisingSEQ ID NOs: 4599 and 4821), ds-siNA-218 (sense and antisenserespectively comprising SEQ ID NOs: 4600 and 4822), ds-siNA-219 (senseand antisense respectively comprising SEQ ID NOs: 4601 and 4823),ds-siNA-220 (sense and antisense respectively comprising SEQ ID NOs:4602 and 4824), ds-siNA-221 (sense and antisense respectively comprisingSEQ ID NOs: 4603 and 4825), and ds-siNA-222 (sense and antisenserespectively comprising SEQ ID NOs: 4604 and 4826). In some embodiments,the siNA is selected from ds-siNA-196 (sense and antisense respectivelycomprising SEQ ID NOs: 4578 and 4800), ds-siNA-197 (sense and antisenserespectively comprising SEQ ID NOs: 4579 and 4801), ds-siNA-198 (senseand antisense respectively comprising SEQ ID NOs: 4580 and 4802), andds-siNA-199 (sense and antisense respectively comprising SEQ ID NOs:4581 and 4803). In some embodiments, the siNA is selected from,ds-siNA-217 (sense and antisense respectively comprising SEQ ID NOs:4599 and 4821), ds-siNA-218 (sense and antisense respectively comprisingSEQ ID NOs: 4600 and 4822), ds-siNA-219 (sense and antisenserespectively comprising SEQ ID NOs: 4601 and 4823), ds-siNA-220 (senseand antisense respectively comprising SEQ ID NOs: 4602 and 4824),ds-siNA-221 (sense and antisense respectively comprising SEQ ID NOs:4603 and 4825), and ds-siNA-222 (sense and antisense respectivelycomprising SEQ ID NOs: 4604 and 4826). In some embodiments, the(3-coronavirus can be SARS-CoV-2. In some embodiments, theβ-coronavirus-caused disease can be COVID-19.

In some embodiments of the disclosed methods and uses, the subject is amammal. In some embodiments, the subject is a human. In someembodiments, the subject is a non-human primate. In some embodiments,the subject is a cat. In some embodiments, the subject is a camel.

In some embodiments of the disclosed methods and uses, the siNA isadministered intravenously, subcutaneously, or via inhalation.

In some embodiments of the disclosed methods and uses, the subject hasbeen treated with one or more additional coronavirus treatment agents.In some embodiments of the disclosed methods, the subject isconcurrently treated with one or more additional coronavirus treatmentagents.

The foregoing general description and following detailed description areexemplary and explanatory and are intended to provide furtherexplanation of the disclosure as claimed. Other objects, advantages, andnovel features will be readily apparent to those skilled in the art fromthe following brief description of the drawings and detailed descriptionof the disclosure.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 (FIG. 1 ) shows the coronaviridae family and its four genera (toppanel) and the full length genome of NCBI 407 (bottom panel), whichencodes 28 proteins across multiple open reading frames (ORF s).

FIG. 2 (FIG. 2 ) shows the percent identity between multiplecoronavirus, including sudden acute respiratory syndrome coronavirus(SARS-CoV), Middle East respiratory syndrome coronavirus (MERS-CoV), andhuman coronavirus OC43 (top panel), and an alignment of the highlysimilar region of the genomes encodings non-structural protein 8 (nsp8)to non-structural protein (nsp15) (bottom panel).

FIG. 3 (FIG. 3 ) shows details of nsp8-nsp15.

FIG. 4 (FIG. 4 ) shows an exemplary siNA molecule.

FIG. 5 (FIG. 5 ) shows an exemplary siNA molecule.

FIGS. 6A-6I (FIGS. 6A-6I) show exemplary double-stranded siNA molecules.

DETAILED DESCRIPTION

Disclosed herein are short interfering nucleic acid (siNA) molecules. Insome embodiments, the siNA is a double-stranded siNA (ds-siNA). In someembodiments, the ds-siNA comprises a sense strand and an antisensestrand. In some embodiments, the ds-siNA comprises (a) a sense strandcomprising a first nucleotide sequence, wherein the first nucleotidesequence is 15 to 30 nucleotides in length; and (b) an antisense strandcomprising a second nucleotide sequence, wherein the second nucleotidesequence is 15 to 30 nucleotides in length and comprises a nucleotidesequence that is the reverse complement of the first nucleotidesequence.

Further disclosed herein are pharmaceutical compositions comprising theds-siNA according to any one of the embodiments described herein and apharmaceutically acceptable carrier or diluent. In some embodiments thedisclosed compositions may comprise two or more ds-siNA according to anyof the embodiments described herein.

Further disclosed herein is a method for treating a disease in a subjectin need thereof, comprising administering the subject one or more siNAor pharmaceutical compositions of any of the embodiments describedherein. In some embodiments, the disease is a viral infection, such as acoronavirus infection (e.g., COVID-19).

Further disclosed herein is the use of one or more ds-siRNA according toany of the embodiments described herein in the manufacture of amedicament for treating a disease, such as a viral infection or, morespecifically, a coronavirus infection (e.g., COVID-19).

Further disclosed herein is a method for treating a disease in a subjectin need thereof, comprising administering the subject one or moreds-siNA or pharmaceutical compositions of any of the embodimentsdescribed herein.

Further disclosed herein is a method of treating a β-coronavirus-causeddisease (e.g., COVID-19) in a subject in need thereof, comprisingadministering the subject one or more ds-siNA according to any of theembodiments described herein.

As described in more detail below, the disclose siNA molecules maycomprise modified nucleotides. The modified nucleotides may be selectedfrom 2′-O-methyl nucleotides and 2′-fluoro nucleotides. The siNAmolecules described herein may comprise 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10or more phosphorothioate internucleoside linkages. The siNA moleculesdescribed herein may comprise at least one phosphorylation blocker. ThesiNA molecules described herein may comprise a 5′-stabilized end cap.The siNA molecules described herein may comprise one or more blunt ends.The siNA molecules described herein may comprise one or more overhangs.

Further, the disclosed siNA molecules may comprise (a) a phosphorylationblocker; and (b) a siNA. The siNA may comprise at least 5 nucleotides.The nucleotides may be modified nucleotides, non-modified nucleotides,or any combination thereof. The nucleotides may be ribonucleotides,deoxyribonucleotides, or any combination thereof. The siNA may besingle-stranded. Alternatively, the siNA is double-stranded. Thedouble-stranded siNA may comprise one or more blunt ends. Thedouble-stranded siNA may comprise one or more overhangs. Thedouble-stranded siNA may comprise a blunt end and an overhang.

Further, the disclosed siNA molecules may comprise (a) a conjugatedmoiety; and (b) a siNA. The siNA may comprise at least 5 nucleotides.The nucleotides may be modified nucleotides, non-modified nucleotides,or any combination thereof. The nucleotides may be ribonucleotides,deoxyribonucleotides, or any combination thereof. The siNA may besingle-stranded. Alternatively, the siNA is double-stranded. Thedouble-stranded siNA may comprise one or more blunt ends. Thedouble-stranded siNA may comprise one or more overhangs. Thedouble-stranded siNA may comprise a blunt end and an overhang.

Further, the disclosed siNA molecules may comprise (a) a 5′-stabilizedend cap; and (b) a siNA. The siNA may comprise at least 5 nucleotides.The nucleotides may be modified nucleotides, non-modified nucleotides,or any combination thereof. The nucleotides may be ribonucleotides,deoxyribonucleotides, or any combination thereof. The siNA may besingle-stranded. Alternatively, the siNA is double-stranded. Thedouble-stranded siNA may comprise one or more blunt ends. Thedouble-stranded siNA may comprise one or more overhangs. Thedouble-stranded siNA may comprise a blunt end and an overhang.

Further, the disclosed siNA molecules may comprise (a) at least onephosphorylation blocker, conjugated moiety, or 5′-stabilized end cap;and (b) a siNA. The siNA may comprise at least 5 nucleotides. Thenucleotides may be modified nucleotides, non-modified nucleotides, orany combination thereof. The nucleotides may be ribonucleotides,deoxyribonucleotides, or any combination thereof. The siNA may besingle-stranded. Alternatively, the siNA is double-stranded. Thedouble-stranded siNA may comprise one or more blunt ends. Thedouble-stranded siNA may comprise one or more overhangs. Thedouble-stranded siNA may comprise a blunt end and an overhang.

Exemplary siNA, which may be used to treat and/or prevent coronavirusinfections (e.g., COVID-19) are also described herein.

Definitions

It is to be understood that methods are not limited to the particularembodiments described, and as such may vary. It is also to be understoodthat the terminology used herein is for the purpose of describingparticular embodiments only and is not intended to be limiting. Thescope of the present technology will be limited only by the appendedclaims.

Unless defined otherwise, all technical and scientific terms used hereinhave the same meaning as commonly understood by one of ordinary skill inthe art to which this invention belongs. Although any methods andmaterials similar or equivalent to those described herein can also beused in the practice or testing of the present invention, representativeillustrative methods and materials are now described.

Where a range of values is provided, it is understood that eachintervening value, to the tenth of the unit of the lower limit unlessthe context clearly dictates otherwise, between the upper and lowerlimit of that range and any other stated or intervening value in thatstated range, is encompassed within the invention. The upper and lowerlimits of these smaller ranges may independently be included in thesmaller ranges and are also encompassed within the invention, subject toany specifically excluded limit in the stated range. Where the statedrange includes one or both of the limits, ranges excluding either orboth of those included limits are also included in the invention.

As used in the specification and claims, the singular form “a,” “an” and“the” include singular and plural references unless the context clearlydictates otherwise.

As used herein, the term “comprising” is intended to mean that thecompositions and methods include the recited elements, but not excludingothers. “Consisting essentially of” when used to define compositions andmethods, shall mean excluding other elements of any essentialsignificance to the composition or method. “Consisting of” shall meanexcluding more than trace elements of other ingredients for claimedcompositions and substantial method steps. Embodiments defined by eachof these transition terms are within the scope of this disclosure.Accordingly, it is intended that the methods and compositions caninclude additional steps and components (comprising) or alternativelyincluding steps and compositions of no significance (consistingessentially of) or alternatively, intending only the stated method stepsor compositions (consisting of).

As used herein, “about” means plus or minus 10% as well as the specifiednumber. For example, “about 10” should be understood as both “10” and“9-11.”

As used herein, “optional” or “optionally” means that the subsequentlydescribed event or circumstance may or may not occur, and that thedescription includes instances where said event or circumstance occursand instances where it does not.

The terms “individual,” “subject,” and “patient” are usedinterchangeably herein, and refer to any individual mammal, e.g.,bovine, canine, feline, equine, simian, porcine, camelid, bat, or human,being treated according to the disclosed methods or uses. In preferredembodiments, the subject is a human.

As used herein, the phrases “effective amount,” “therapeuticallyeffective amount,” and “therapeutic level” mean the siNA dosage orconcentration in a subject that provides the specific pharmacologicaleffect for which the siNA is administered in a subject in need of suchtreatment, i.e. to treat or prevent a coronavirus infection (e.g., MERS,SARS, or COVID-19). It is emphasized that a therapeutically effectiveamount or therapeutic level of an siNA will not always be effective intreating the infections described herein, even though such dosage isdeemed to be a therapeutically effective amount by those of skill in theart. For convenience only, exemplary dosages, drug delivery amounts,therapeutically effective amounts, and therapeutic levels are providedbelow. Those skilled in the art can adjust such amounts in accordancewith standard practices as needed to treat a specific subject and/orcondition. The therapeutically effective amount may vary based on theroute of administration and dosage form, the age and weight of thesubject, and/or the subject's condition, including the type and severityof the coronavirus infection.

The terms “treatment” or “treating” as used herein with reference to acoronavirus infections refer to reducing or eliminating viral loadand/or improving or ameliorating one or more symptoms of an infectionsuch as cough, shortness of breath, body aches, chills, and/or fever.

The terms “prevent” or “preventing” as used herein with reference to acoronavirus infections refer to precluding an infection from developingin a subject exposed to a coronavirus and/or avoiding the development ofone or more symptoms of an infection such as cough, shortness of breath,body aches, chills, and/or fever. “Prevention” may occur when the viralload is never allowed to exceed beyond a threshold level at which pointthe subject begins to feel sick or exhibit symptoms. “Prevention” mayalso, in some embodiments, refer to the prevention of a subsequentinfection once an initial infection has been treated or cured.

As used herein, the term “pharmaceutical composition” refers to thecombination of an active agent with a carrier, inert or active, makingthe composition especially suitable for diagnostic or therapeutic use invivo or ex vivo.

As used herein, the term “pharmaceutically acceptable carrier” refers toany of the standard pharmaceutical carriers, such as a phosphatebuffered saline solution, water, emulsions (e.g., such as an oil/wateror water/oil emulsions), and various types of wetting agents. Thecompositions also can include stabilizers and preservatives. Forexamples of carriers, stabilizers and adjuvants, see, for example,Martin, Remington's Pharmaceutical Sciences, 15th Ed., Mack Publ. Co.,Easton, Pa. [1975].

The phrases “parenteral administration” and “administered parenterally”as used herein means modes of administration other than enteral andtopical administration, usually by injection, and includes, withoutlimitation, intravenous, intramuscular, intraarterial, intrathecal,intracapsular, intraorbital, intracardiac, intradermal, intraperitoneal,transtracheal, subcutaneous, subcuticular, intraarticular, subcapsular,subarachnoid, intraspinal and intrasternal injection and infusion.

The phrases “systemic administration,” “administered systemically,”“peripheral administration” and “administered peripherally” as usedherein mean the administration of a compound, drug or other materialother than directly into the central nervous system, such that it entersthe patient's system and, thus, is subject to metabolism and other likeprocesses, for example, subcutaneous administration.

As used herein, the term “nucleobase” refers to a nitrogen-containingbiological compound that forms a nucleoside. Examples of nucleobasesinclude, but are not limited to, thymine, uracil, adenine, cytosine,guanine, aryl, heteroaryl, and an analogue or derivative thereof.

The target gene may be any gene in a cell or virus. Here, “target gene”and “target sequence” are used synonymously.

For the purposes of the present disclosure, a DNA sequence that replacesall the U residues of an RNA sequence with T residues is “identical” tothe RNA sequence, and vice versa. Accordingly, a sequence that is“identical to an RNA corresponding to” a DNA sequence constitutes theDNA sequence with all T replaced by U. The presence of modifiednucleotides or 2′-deoxynucleotides in a sequence does not make asequence not “identical to an RNA” but rather a modified RNA.

As used herein, “modified nucleotide” includes any nucleic acid ornucleic acid analogue residue that contains a modification orsubstitution in the chemical structure of an unmodified nucleotide base,sugar (including, but not limited to, 2′-substitution), or phosphate(including, but not limited to, alternate internucleotide linkers, suchas phosphorothioates or the substitution of bridging oxygens inphosphate linkers with bridging sulfurs), or a combination thereof.Non-limiting examples of modified nucleotides are shown herein.

As used herein, the term “d2vd3 nucleotide” refers to a nucleotidecomprising a 5′-stabilized end cap of Formula (10):

Throughout the description, where compositions are described as having,including, or comprising specific components, or where processes andmethods are described as having, including, or comprising specificsteps, it is contemplated that, additionally, there are compositions ofthe present disclosure that consist essentially of, or consist of, therecited components, and that there are processes and methods accordingto the present disclosure that consist essentially of, or consist of,the recited processing steps.

As a general matter, compositions specifying a percentage are by weightunless otherwise specified. Further, if a variable is not accompanied bya definition, then the previous definition of the variable controls.

Coronaviruses and Coronavirus Infections

The siNA molecules and compositions described herein may be administeredto a subject to treat a disease. Further disclosed herein are uses ofany of the siNA molecules or compositions disclosed herein in themanufacture of a medicament for treating a disease.

In some embodiments of the disclosed method and uses, the disease beingtreated is a viral disease. In some embodiments, the viral disease iscaused by an RNA virus. In some embodiments, the RNA virus is asingle-stranded RNA virus (ssRNA virus). In some embodiments, the ssRNAvirus is a positive-sense single-stranded RNA virus ((+)ssRNA virus). Insome embodiments, the (+)ssRNA virus is a coronavirus.

Coronaviruses are a family of viruses (i.e., the coronaviridae family)that cause respiratory infections in mammals and that comprise a genomethat is roughly 30 kilobases in length. The coronaviridae family isdivided into four genera and the genome encodes 28 proteins acrossmultiple open reading frames, including 16 non-structural proteins (nsp)that are post-translationally cleaved from a polyprotein (see FIG. 1 ).

The coronaviridae family includes both α-coronaviruses orβ-coronaviruses, which both mainly infect bats, but can also infectother mammals like humans, camels, and rabbits. β-coronaviruses have, todate, been of greater clinical importance, having caused epidemicsincluding severe acute respiratory syndrome (SARS), Middle Eastrespiratory syndrome (MERS), and COVID-19. Other disease-causingβ-coronaviruses include OC44, and HKU1. Non-limiting examples ofdisease-causing α-coronaviruses include, but are not limited to, 229Eand NL63.

In some embodiments, the coronavirus is a β-coronaviruses. In someembodiments, the β-coronaviruses is selected from the group consistingof severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) (alsoknown by the provisional name 2019 novel coronavirus, or 2019-nCoV),human coronavirus OC43 (hCoV-OC43), Middle East respiratorysyndrome-related coronavirus (MERS-CoV, also known by the provisionalname 2012 novel coronavirus, or 2012-nCoV), and severe acute respiratorysyndrome-related coronavirus (SARS-CoV, also known as SARS-CoV-1). Insome embodiments, the β-coronaviruses is SARS-CoV-2, the causative agentof COVID-19.

As shown in FIGS. 2 and 3 , several disease-causing coronaviruses sharea high degree of homology in the regions of the genome encodingnon-structural proteins (nsp), and more specifically, in the regionencoding nsp8-nsp15. Indeed, there is roughly 65% identity across theroughly 7 kB sequence of β-coronaviruses from about nucleotide 12900 toabout nucleotide 19900 of 2019-nCoV, and some subsections of the genomicspan of nsp8 to nsp15 may comprise 95% or more identity. All of thegenes in this region encode non-structural proteins associated withreplication. Accordingly, this segment of the genome is suitable fortargeting with an siNA that can provide a broad spectrum treatment formultiple different types of coronavirus, such as MERS-CoV, SARS-CoV-1,and SARS-CoV-2.

Without wishing to be bound by theory, upon entry into a cell, any ofthe ds-siNA molecules disclosed herein may interact with proteins in thecell to form a RNA-Induced Silencing Complex (RISC). Once the ds-siNA ispart of the RISC, the ds-siNA may be unwound to form a single-strandedsiNA (ss-siNA). The ss-siNA may comprise the antisense strand of theds-siNA. The antisense strand may bind to a complementary messenger RNA(mRNA), which results in silencing of the gene that encodes the mRNA.

In some embodiments, the target gene is a viral gene. In someembodiments, the viral gene is from an RNA virus. In some embodiments,the RNA virus is a single-stranded RNA virus (ssRNA virus). In someembodiments, the ssRNA virus is a positive-sense single-stranded RNAvirus ((+)ssRNA virus). In some embodiments, the (+)ssRNA virus is acoronavirus. In some embodiments, the coronavirus is a β-coronavirus. Insome embodiments, the β-coronavirus is severe acute respiratory syndromecoronavirus 2 (SARS-CoV-2) (also known by the provisional name 2019novel coronavirus, or 2019-nCoV), human coronavirus OC43 (hCoV-OC43),Middle East respiratory syndrome-related coronavirus (MERS-CoV, alsoknown by the provisional name 2012 novel coronavirus, or 2012-nCoV),severe acute respiratory syndrome-related coronavirus (SARS-CoV, alsoknown as SARS-CoV-1). In some embodiments, the β-coronavirus isSARS-CoV-2.

In some embodiments, the target gene is selected from genome ofSARS-CoV-2. In some embodiments, SARS-CoV-2 has a genome sequence shownin the nucleotide sequence of SEQ ID NO: 2407, which corresponds to thenucleotide sequence of GenBank Accession No. NC_045512.2, which isincorporated by reference in its entirety.

In some embodiments, the target gene is selected from genome ofSARS-CoV. In some embodiments, SARS-CoV has a genome sequence shown inthe nucleotide sequence of SEQ ID NO: 2408, which corresponds to thenucleotide sequence of GenBank Accession No. NC_004718.3, which isincorporated by reference in its entirety.

In some embodiments, the target gene is selected from the genome ofMERS-CoV. In some embodiments, MERS-CoV has a genome sequence shown inthe nucleotide sequence of SEQ ID NO: 2409, which corresponds to thenucleotide sequence of GenBank Accession No. NC_019843.3, which isincorporated by reference in its entirety.

In some embodiments, the target gene is selected from the genome ofhCoV-OC43. In some embodiments, hCoV-OC43 has a genome sequence shown inthe nucleotide sequence of SEQ ID NO: 2410, which corresponds to thenucleotide sequence of GenBank Accession No. NC_006213.1, which isincorporated by reference in its entirety.

Short Interfering Nucleic Acid (siNA) Molecules

As indicated above, the present disclosure provides siNA moleculescomprising modified nucleotides. Any of the siNA molecules describedherein may be double-stranded siNA (ds-siNA) molecules. The terms “siNAmolecules” and “ds-siNA molecules” may be used interchangeably. In someembodiments, the ds-siNA molecules comprise a sense strand and anantisense strand.

The disclosed siNA molecules may comprise (a) at least onephosphorylation blocker, conjugated moiety, or 5′-stabilized end cap;and (b) a short interfering nucleic acid (siNA). In some embodiments,the phosphorylation blocker is a phosphorylation blocker disclosedherein. In some embodiments, the 5′-stabilized end cap is a5′-stabilized end cap disclosed herein. The siNA may comprise any of thefirst nucleotide, second nucleotide, sense strand, or antisense strandsequences disclosed herein. The siNA may comprise 5 to 100, 5 to 90, 10to 100, 10 to 90, 10 to 80, 10 to 70, 10 to 60, 10 to 50, 10 to 30, 10to 25, 15 to 100, 15 to 90, 15 to 80, 15 to 70, 15 to 60, 15 to 50, 15to 30, or 15 to 25 nucleotides. The siNA may comprise at least 5, 10,11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28,29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, or 40 nucleotides. The siNAmay comprise less than or equal to 50, 45, 40, 39, 38, 37, 36, 35, 34,33, 32, 31, 30, 29, 28, 27, 26, 25, 24, 23, 22, 21, 20, or 19nucleotides. The nucleotides may be modified nucleotides. The siNA maybe single stranded. The siNA may be double stranded. The siNA maycomprise (a) a sense strand comprising 15 to 30, 15 to 25, 15 to 24, 15to 23, 15 to 22, 15 to 21, 17 to 30, 17 to 25, 17 to 24, 17 to 23, 17 to22, 17 to 21, 18 to 30, 18 to 25, 18 to 24, 18 to 23, 18 to 22, 18 to21, 19 to 30, 19 to 25, 19 to 24, 19 to 23, 19 to 22, 19 to 21, 20 to25, 20 to 24, 20 to 23, 21 to 25, 21 to 24, or 21 to 23 nucleotides; and(b) an antisense strand comprising 15 to 30, 15 to 25, 15 to 24, 15 to23, 15 to 22, 15 to 21, 17 to 30, 17 to 25, 17 to 24, 17 to 23, 17 to22, 17 to 21, 18 to 30, 18 to 25, 18 to 24, 18 to 23, 18 to 22, 18 to21, 19 to 30, 19 to 25, 19 to 24, 19 to 23, 19 to 22, 19 to 21, 20 to25, 20 to 24, 20 to 23, 21 to 25, 21 to 24, or 21 to 23 nucleotides. ThesiNA may comprise (a) a sense strand comprising about 15, 16, 17, 18,19, 20, 21, 22, or 23 nucleotides; and (b) an antisense strandcomprising about 15, 16, 17, 18, 19, 20, 21, 22, or 23 nucleotides. ThesiNA may comprise (a) a sense strand comprising about 19 nucleotides;and (b) an antisense strand comprising about 21 nucleotides. The siNAmay comprise (a) a sense strand comprising about 21 nucleotides; and (b)an antisense strand comprising about 23 nucleotides.

In some embodiments, any of the siNA molecules disclosed herein furthercomprise one or more linkers independently selected from aphosphodiester (PO) linker, phosphorothioate (PS) linker,phosphorodithioate linker, and PS-mimic linker. In some embodiments, thePS-mimic linker is a sulfur linker. In some embodiments, the linkers areinternucleotide linkers. Alternatively, or additionally, the linkersconnect a nucleotide of the siNA molecule to at least onephosphorylation blocker, conjugated moiety, or 5′-stabilized end cap. Insome embodiments, the linkers connect a conjugated moiety to aphosphorylation blocker or 5′-stabilized end cap.

Table 1 details sequences of the present disclosure useful for sense andantisense strands, disclosed in SEQ ID NOs: 1-2406 and 3393-4374. Table2 details representative genome sequences of four pathogenicβ-coronaviruses, disclosed in SEQ ID NOs: 2407-2410. It is understoodthat RNA sequences corresponding to these sequences constitute identicalsequences with all T replaced with U.

In some embodiments, the target gene a sequence 15 to 30, 15 to 25, 15to 23, 17 to 23, 19 to 23, or 19 to 21 nucleotides in length, andpreferably 19 or 21 nucleotides in length, within a region of eithertwo, three, or four of SEQ ID NOs: 2407, 2408, 2409, and 2410. In someembodiments, the first nucleotide sequence is identical to an RNAsequence corresponding to a region of each of SEQ ID NOs: 2407, 2408,2409, and 2410. In some embodiments, the target gene a sequence 15 to30, 15 to 25, 15 to 23, 17 to 23, 19 to 23, or 19 to 21 nucleotides inlength, and preferably 19 or 21 nucleotides in length, within a regionof either two, three, or four of the genomes of severe acute respiratorysyndrome coronavirus 2 (SARS-CoV-2), human coronavirus OC43 (hCoV-OC43),Middle East respiratory syndrome-related coronavirus (MERS-CoV), andsevere acute respiratory syndrome-related coronavirus (SARS-CoV). Insome embodiments, the first nucleotide sequence is identical to an RNAsequence corresponding to a region of each of two, three, or four of thegenomes of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2),human coronavirus OC43 (hCoV-OC43), Middle East respiratorysyndrome-related coronavirus (MERS-CoV), and severe acute respiratorysyndrome-related coronavirus (SARS-CoV). In some embodiments, the firstnucleotide sequence is identical to the target gene. In someembodiments, the second nucleotide sequence is complementary to thetarget gene.

In some embodiments, the second nucleotide sequence is complementary toa sequence within a region of either two, three, or four of SEQ ID NOs:2407, 2408, 2409, and 2410. In some embodiments, the second nucleotidesequence is complementary to an RNA sequence corresponding to a regionof each of SEQ ID NOs: 2407, 2408, 2409, and 2410. In some embodiments,the second nucleotide sequence comprises a sequence corresponding to oneof SEQ ID NOs: 1204-2406 and 3393-4374.

In some embodiments, the second nucleotide is complementary to anucleotide region within SEQ ID NO: 2407, 2408, 2409, or 2410. In someembodiments, the second nucleotide sequence is complementary to 15 to30, 15 to 25, 15 to 23, 15 to 22, 15 to 21, 17 to 25, 17 to 23, 17 to22, 17 to 21, or 19 to 21 nucleotides, and preferably 19 to 21nucleotides, and more preferably 19 or 21 nucleotides, within positions190-216, 233-279, 288-324, 455-477, 626-651, 704-723, 3352-3378,5384-5403, 6406-6483, 7532-7551, 9588-9606, 10484-10509, 11609-11630,11834-11853, 12023-12045, 12212-12234, 12401-12420, 12839-12867,12885-12924, 12966-12990, 13151-13176, 13363-13386, 13388-13416,13458-13416, 13458-13520, 13762-13790, 14290-14312, 14404-14429,14500-14531, 14623-14642, 14650-14687, 14698-14717, 14722-14748,14750-14777, 14821-14846, 14854-14873, 14875-14903, 14962-14990,14992-15020, 15055-15140, 15172-15200, 15310-15332, 15346-15367,15496-15518, 15622-15644, 15838-15869, 15886-15905, 15985-16010,16057-16079, 16186-16205, 16430-16448, 16822-16865, 16954-16976,17008-17042, 17080-17111, 17137-17156, 17269-17289, 17530-17549,17563-17582, 17680-17699, 17746-17765, 17857-17876, 17956-17975,18100-18122, 18196-18218, 19618-19639, 19783-19802, 19831-19850,20107-20130, 20776-20795, 21502-21524, 24302-24325, 24446-24465,24620-24651, 24662-24684, 25034-25057, 25104-25128, 25364-25387,25502-25530, 26191-26227, 26232-26267, 26269-26330, 26332-26394,26450-26481, 26574-26600, 27003-27064, 27093-27111, 27183-27212,27382-27407, 27511-27533, 27771-27818, 28270-28296, 28397-28434,28513-28546, 28673-28692, 28706-28726, 28744-28794, 28799-28827,28946-28972, 28976-29034, 29144-29172, 29174-29196, 29228-29259,29285-29305, 29342-29394, 29444-29463, 29543-29566, 29598-29630,29652-29687, 29689-29731, 29733-29757, or 29770-29828 of SEQ ID NO:2407. In some embodiments, the second nucleotide sequence iscomplementary to any one of SEQ ID NOs: 1-1203 and 2411-3392. In someembodiments, the second nucleotide sequence is identical to an RNAcorresponding to any one of SEQ ID NOs: 1204-2406 and 3393-4374.

In some embodiments, the first nucleotide sequence is identical to anucleotide region within SEQ ID NOs: 2407, 2408, 2409, or 2410, with theexception that the thymines (Ts) in SEQ ID NOs: 2407, 2408, 2409, or2410 are replaced with uracil (U). In some embodiments, the firstnucleotide sequence is identical to 15 to 30, 15 to 25, 15 to 23, 15 to22, 15 to 21, 17 to 25, 17 to 23, 17 to 22, 17 to 21, or 19 to 21nucleotides, and preferably 19 to 21 nucleotides, and more preferably 19or 21 nucleotides, within positions 190-216, 233-279, 288-324, 455-477,626-651, 704-723, 3352-3378, 5384-5403, 6406-6483, 7532-7551, 9588-9606,10484-10509, 11609-11630, 11834-11853, 12023-12045, 12212-12234,12401-12420, 12839-12867, 12885-12924, 12966-12990, 13151-13176,13363-13386, 13388-13416, 13458-13416, 13458-13520, 13762-13790,14290-14312, 14404-14429, 14500-14531, 14623-14642, 14650-14687,14698-14717, 14722-14748, 14750-14777, 14821-14846, 14854-14873,14875-14903, 14962-14990, 14992-15020, 15055-15140, 15172-15200,15310-15332, 15346-15367, 15496-15518, 15622-15644, 15838-15869,15886-15905, 15985-16010, 16057-16079, 16186-16205, 16430-16448,16822-16865, 16954-16976, 17008-17042, 17080-17111, 17137-17156,17269-17289, 17530-17549, 17563-17582, 17680-17699, 17746-17765,17857-17876, 17956-17975, 18100-18122, 18196-18218, 19618-19639,19783-19802, 19831-19850, 20107-20130, 20776-20795, 21502-21524,24302-24325, 24446-24465, 24620-24651, 24662-24684, 25034-25057,25104-25128, 25364-25387, 25502-25530, 26191-26227, 26232-26267,26269-26330, 26332-26394, 26450-26481, 26574-26600, 27003-27064,27093-27111, 27183-27212, 27382-27407, 27511-27533, 27771-27818,28270-28296, 28397-28434, 28513-28546, 28673-28692, 28706-28726,28744-28794, 28799-28827, 28946-28972, 28976-29034, 29144-29172,29174-29196, 29228-29259, 29285-29305, 29342-29394, 29444-29463,29543-29566, 29598-29630, 29652-29687, 29689-29731, 29733-29757, or29770-29828 of SEQ ID NO: 2407. In some embodiments, the firstnucleotide sequence is identical to an RNA corresponding to any one ofSEQ ID NOs: 1-1203 and 2411-3392. In some embodiments, the firstnucleotide sequence is complementary to any one of SEQ ID NOs: 1204-2406and 3393-4374.

An exemplary siNA molecule of the present disclosure is shown in FIG. 4. As shown in FIG. 4 , an exemplary siNA molecule can comprise a sensestrand (101) and an antisense strand (102). The sense strand (101) maycomprise a first oligonucleotide sequence (103). The firstoligonucleotide sequence (103) may comprise one or more phosphorothioateinternucleoside linkages (109). The phosphorothioate internucleosidelinkage (109) may be between the nucleotides at the 5′ or 3′ terminalend of the first oligonucleotide sequence (103). The phosphorothioateinternucleoside linkage (109) may be between the first three nucleotidesfrom the 5′ end of the first oligonucleotide sequence (103). The firstoligonucleotide sequence (103) may comprise one or more 2′-fluoronucleotides (110). The first oligonucleotide sequence (103) may compriseone or more 2′-O-methyl nucleotides (111). The first oligonucleotidesequence (103) may comprise 15 or more modified nucleotidesindependently selected from 2′-fluoro nucleotides (110) and 2′-O-methylnucleotides (111). The sense strand (101) may further comprise aphosphorylation blocker (105). The sense strand (101) may furthercomprise an optional conjugated moiety (106). The antisense strand (102)may comprise a second oligonucleotide sequence (104). The secondoligonucleotide sequence (104) may comprise one or more phophorothioateinternucleoside linkages (109). The phosphorothioate internucleosidelinkage (109) may be between the nucleotides at the 5′ or 3′ terminalend of the second oligonucleotide sequence (104). The phosphorothioateinternucleoside linkage (109) may be between the first three nucleotidesfrom the 5′ end of the second oligonucleotide sequence (104). Thephosphorothioate internucleoside linkage (109) may be between the firstthree nucleotides from the 3′ end of the second oligonucleotide sequence(104). The second oligonucleotide sequence (104) may comprise one ormore 2′-fluoro nucleotides (110). The second oligonucleotide sequence(104) may comprise one or more 2′-O-methyl nucleotides (111). The secondoligonucleotide sequence (104) may comprise 15 or more modifiednucleotides independently selected from 2′-fluoro nucleotides (110) and2′-O-methyl nucleotides (111). The antisense strand (102) may furthercomprise a 5′-stabilized end cap (107). The siNA may further compriseone or more blunt ends. Alternatively, or additionally, one end of thesiNA may comprise an overhang (108). The overhang (108) may be part ofthe sense strand (101). The overhang (108) may be part of the antisensestrand (102). The overhang (108) may be distinct from the firstnucleotide sequence (103). The overhang (108) may be distinct from thesecond nucleotide sequence (104). The overhang (108) may be part of thefirst nucleotide sequence (103). The overhang (108) may be part of thesecond nucleotide sequence (104). The overhang (108) may comprise 1 ormore nucleotides. The overhang (108) may comprise 1 or moredeoxyribonucleotides. The overhang (108) may comprise 1 or more modifiednucleotides. The overhang (108) may comprise 1 or more modifiedribonucleotides. The sense strand (101) may be shorter than theantisense strand (102). The sense strand (101) may be the same length asthe antisense strand (102). The sense strand (101) may be longer thanthe antisense strand (102).

Another exemplary siNA molecule of the present disclosure is shown inFIG. 5 . As shown in FIG. 5 , an exemplary siNA molecule can comprise asense strand (201) and an antisense strand (202). The sense strand (201)may comprise a first oligonucleotide sequence (203). The firstoligonucleotide sequence (203) may comprise one or more phophorothioateinternucleoside linkages (209). The phosphorothioate internucleosidelinkage (209) may be between the nucleotides at the 5′ or 3′ terminalend of the first oligonucleotide sequence (203). The phosphorothioateinternucleoside linkage (209) may be between the first three nucleotidesfrom the 5′ end of the first oligonucleotide sequence (203). The firstoligonucleotide sequence (203) may comprise one or more 2′-fluoronucleotides (210). The first oligonucleotide sequence (203) may compriseone or more 2′-O-methyl nucleotides (211). The first oligonucleotidesequence (203) may comprise 15 or more modified nucleotidesindependently selected from 2′-fluoro nucleotides (210) and 2′-O-methylnucleotides (211). The sense strand (201) may further comprise aphosphorylation blocker (205). The sense strand (201) may furthercomprise an optional conjugated moiety (206). The antisense strand (202)may comprise a second oligonucleotide sequence (204). The secondoligonucleotide sequence (204) may comprise one or more phophorothioateinternucleoside linkages (209). The phosphorothioate internucleosidelinkage (209) may be between the nucleotides at the 5′ or 3′ terminalend of the second oligonucleotide sequence (204). The phosphorothioateinternucleoside linkage (209) may be between the first three nucleotidesfrom the 5′ end of the second oligonucleotide sequence (204). Thephosphorothioate internucleoside linkage (209) may be between the firstthree nucleotides from the 3′ end of the second oligonucleotide sequence(204). The second oligonucleotide sequence (204) may comprise one ormore 2′-fluoro nucleotides (210). The second oligonucleotide sequence(204) may comprise one or more 2′-O-methyl nucleotides (211). The secondoligonucleotide sequence (204) may comprise 15 or more modifiednucleotides independently selected from 2′-fluoro nucleotides (210) and2′-O-methyl nucleotides (211). The antisense strand (202) may furthercomprise a 5′-stabilized end cap (207). The siNA may further compriseone or more overhangs (208). The overhang (208) may be part of the sensestrand (201). The overhang (208) may be part of the antisense strand.(202). The overhang (208) may be distinct from the first nucleotidesequence (203). The overhang (208) may be distinct from the secondnucleotide sequence (204). The overhang (208) may be part of the firstnucleotide sequence (203). The overhang (208) may be part of the secondnucleotide sequence (204). The overhang (208) may be adjacent to the 3′end of the first nucleotide sequence (203). The overhang (208) may beadjacent to the 5′ end of the first nucleotide sequence (203). Theoverhang (208) may be adjacent to the 3′ end of the second nucleotidesequence (204). The overhang (208) may be adjacent to the 5′ end of thesecond nucleotide sequence (204). The overhang (208) may comprise 1 ormore nucleotides. The overhang (208) may comprise 1 or moredeoxyribonucleotides. The overhang (208) may comprise a TT sequence. Theoverhang (208) may comprise 1 or more modified nucleotides. The overhang(208) may comprise 1 or more modified nucleotides disclosed herein(e.g., 2-fluoro nucleotide, 2′-O-methyl nucleotide, 2′-fluoro nucleotidemimic, 2′-O-methyl nucleotide mimic, or a nucleotide comprising amodified nucleobase). The overhang (208) may comprise 1 or more modifiedribonucleotides. The sense strand (201) may be shorter than theantisense strand (202). The sense strand (201) may be the same length asthe antisense strand (202). The sense strand (201) may be longer thanthe antisense strand (202).

FIGS. 6A-6I depict exemplary ds-siNA modification patterns. As shown inFIGS. 6A-6G, an exemplary ds-siNA molecule may have the followingformula:

5′-A_(n) ¹B_(n) ²A_(n) ³B_(n) ⁴A_(n) ⁵B_(n) ⁶A_(n) ⁷B_(n) ⁸A_(n) ⁹-3′3′-C_(q) ¹A_(q) ²B_(q) ³A_(q) ⁴B_(q) ⁵A_(q) ⁶B_(q) ⁷A_(q) ⁸B_(q) ⁹A_(q)¹⁰B_(q) ¹¹A_(q) ¹²-5′wherein:the top strand is a sense strand comprising a first nucleotide sequencethat is at least about 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, or 100%identical to an RNA corresponding to a target gene, wherein the firstnucleotide sequence comprises 15 to 30 nucleotides;the bottom strand is an antisense strand comprising a second nucleotidesequence that is at least about 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%,or 100% complementary to the RNA corresponding to the target gene,wherein the second nucleotide sequence comprises 15 to 30 nucleotides;each A is independently a 2′-O-methyl nucleotide or a nucleotidecomprising a 5′ stabilized end cap or phosphorylation blocker;B is a 2′-fluoro nucleotide;C represents overhanging nucleotides and is a 2′-O-methyl nucleotide;n¹=1-4 nucleotides in length;each n², n⁶, n⁸, q³, q⁵, q⁷, q⁹, q¹¹, and q¹² is independently 0-1nucleotides in length;each n³ and n⁴ is independently 1-3 nucleotides in length;n⁵ is 1-10 nucleotides in length;n⁷ is 0-4 nucleotides in length;each n⁹, q¹, and q² is independently 0-2 nucleotides in length;q⁴ is 0-3 nucleotides in length;q⁶ is 0-5 nucleotides in length;q⁸ is 2-7 nucleotides in length; andq¹⁰ is 2-11 nucleotides in length.

The ds-siNA may further comprise a conjugated moiety. The ds-siNA mayfurther comprise (i) phosphorothioate internucleoside linkages betweenthe nucleotides at positions 1 and 2 and positions 2 and 3 from the 5′end of the sense strand; and (ii) phosphorothioate internucleosidelinkages between the nucleotides at positions 1 and 2; positions 2 and3; positions 19 and 20; and positions 20 and 21 from the 5′ end of theantisense strand. The ds-siNA may further comprise a 5′-stabilizing endcap. The 5′-stabilizing end cap may be a vinyl phosphonate. The5′-stabilizing end cap may be attached to the 5′ end of the antisensestrand. In some embodiments, the 2′-O-methyl nucleotide at position 1from the 5′ end of the sense strand is further modified to contain a 5′stabilizing end cap. In some embodiments, the 2′-O-methyl nucleotide atposition 1 from the 5′ end of the antisense strand is further modifiedto contain a 5′ stabilizing end cap. In some embodiments, the2′-O-methyl nucleotide at position 1 from the 5′ end of the sense strandis further modified to contain a phosphorylation blocker. In someembodiments, the 2′-O-methyl nucleotide at position 1 from the 3′ end ofthe sense strand is further modified to contain a phosphorylationblocker. In some embodiments, the 2′-O-methyl nucleotide at position 1from the 5′ end of the antisense strand is further modified to contain aphosphorylation blocker. In some embodiments, the 2′-O-methyl nucleotideat position 1 from the 3′ end of the antisense strand is furthermodified to contain a phosphorylation blocker. An exemplary ds-siNAmolecule may have the following formula:

5′-A₂₋₄B₁A₁₋₃B₂₋₃A₂₋₁₀B₀₋₁A₀₋₄B₀₋₁A₀₋₂-3′3′-C₂A₀₋₂B₀₋₁A₀₋₃B₀₋₁A₀₋₅B₀₋₁A₂₋₇B₁A₂₋₁₁B₁A₁-5′wherein:the top strand is a sense strand comprising a first nucleotide sequencethat is at least about 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, or 100%identical to an RNA corresponding to a target gene, wherein the firstnucleotide sequence comprises 15 to 30 nucleotides;the bottom strand is an antisense strand comprising a second nucleotidesequence that is at least about 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%,or 100% complementary to the RNA corresponding to the target gene,wherein the second nucleotide sequence comprises 15 to 30 nucleotides;each A is independently a 2′-O-methyl nucleotide or a nucleotidecomprising a 5′ stabilized end cap or phosphorylation blocker;B is a 2′-fluoro nucleotide;C represents overhanging nucleotides and is a 2′-O-methyl nucleotide.

The ds-siNA may further comprise a conjugated moiety. The ds-siNA mayfurther comprise (i) phosphorothioate internucleoside linkages betweenthe nucleotides at positions 1 and 2 and positions 2 and 3 from the 5′end of the sense strand; and (ii) phosphorothioate internucleosidelinkages between the nucleotides at positions 1 and 2; positions 2 and3; positions 19 and 20; and positions 20 and 21 from the 5′ end of theantisense strand. The ds-siNA may further comprise a 5′-stabilizing endcap. The 5′-stabilizing end cap may be a vinyl phosphonate. The vinylphosphonate may be a deuterated vinyl phosphonate. The deuterated vinylphosphonate may be a mono-deuterated vinyl phosphonate. The deuteratedvinyl phosphonate may be a mono-di-deuterated vinyl phosphonate. The5′-stabilizing end cap may be attached to the 5′ end of the antisensestrand. The 5′-stabilizing end cap may be attached to the 3′ end of theantisense strand. The 5′-stabilizing end cap may be attached to the 5′end of the sense strand. The 5′-stabilizing end cap may be attached tothe 3′ end of the sense strand. In some embodiments, the 2′-O-methylnucleotide at position 1 from the 5′ end of the sense strand is furthermodified to contain a 5′ stabilizing end cap. In some embodiments, the2′-O-methyl nucleotide at position 1 from the 5′ end of the antisensestrand is further modified to contain a 5′ stabilizing end cap. In someembodiments, the 2′-O-methyl nucleotide at position 1 from the 5′ end ofthe sense strand is further modified to contain a phosphorylationblocker. In some embodiments, the 2′-O-methyl nucleotide at position 1from the 3′ end of the sense strand is further modified to contain aphosphorylation blocker. In some embodiments, the 2′-O-methyl nucleotideat position 1 from the 5′ end of the antisense strand is furthermodified to contain a phosphorylation blocker. In some embodiments, the2′-O-methyl nucleotide at position 1 from the 3′ end of the antisensestrand is further modified to contain a phosphorylation blocker.

The exemplary ds-siNA shown in FIGS. 6A-6I comprise (i) a sense strandcomprising 19-21 nucleotides; and (ii) an antisense strand comprising21-23 nucleotides. The ds-siNA may further comprise (iii) an optionalconjugated moiety, wherein the conjugated moiety is attached to the 3′end of the antisense strand and, in some embodiments, no ps would beneeded at the 3′-end of the sense strand if it is conjugated to a moietyand such conjugation my also result in removal of the 5′ overhang on thesense strand. The ds-siNA may comprise a 2-nucleotide overhangconsisting of nucleotides at positions 20 and 21 from the 5′ end of theantisense strand. The ds-siNA may comprise a 2-nucleotide overhangconsisting of nucleotides at positions 22 and 23 from the 5′ end of theantisense strand. The ds-siNA may further comprise 1, 2, 3, 4, 5, 6 ormore phosphorothioate (ps) internucleoside linkages. At least onephosphorothioate internucleoside linkage may be between the nucleotidesat positions 1 and 2 or positions 2 and 3 from the 5′ end of the sensestrand. At least one phosphorothioate internucleoside linkage may bebetween the nucleotides at positions 1 and 2 or positions 2 and 3 fromthe 5′ end of the antisense strand. At least one phosphorothioateinternucleoside linkage may be between the nucleotides at positions 19and 20, positions 20 and 21, positions 21 and 22, or positions 22 and 23from the 5′ end of the antisense strand. As shown in FIGS. 6A-6G, 4-6nucleotides in the sense strand may be 2′-fluoro nucleotides. As shownin FIGS. 6A-6G, 2-5 nucleotides in the antisense strand may be 2′-fluoronucleotides. As shown in FIGS. 6A-6G, 13-15 nucleotides in the sensestrand may be 2′-O-methyl nucleotides. As shown in FIGS. 6A-6G, 14-19nucleotides in the antisense strand may be 2′-O-methyl nucleotides. Asshown in FIGS. 6A-6G, the ds-siNA does not contain a base pair between2′-fluoro nucleotides on the sense and antisense strands. In someembodiments, the 2′-O-methyl nucleotide at position 1 from the 5′ end ofthe sense strand is further modified to contain a 5′ stabilizing endcap. In some embodiments, the 2′-O-methyl nucleotide at position 1 fromthe 5′ end of the antisense strand is further modified to contain a 5′stabilizing end cap. In some embodiments, the 2′-O-methyl nucleotide atposition 1 from the 5′ end of the sense strand is further modified tocontain a phosphorylation blocker. In some embodiments, the 2′-O-methylnucleotide at position 1 from the 3′ end of the sense strand is furthermodified to contain a phosphorylation blocker. In some embodiments, the2′-O-methyl nucleotide at position 1 from the 5′ end of the antisensestrand is further modified to contain a phosphorylation blocker. In someembodiments, the 2′-O-methyl nucleotide at position 1 from the 3′ end ofthe antisense strand is further modified to contain a phosphorylationblocker.

As shown in FIG. 6A, a ds-siNA may comprise (a) a sense strandconsisting of 21 nucleotides, wherein 2′-fluoro nucleotides are atpositions 3, 7-9, 12, and 17 from the 5′ end of the sense strand, andwherein 2′-O-methyl nucleotides are at positions 1, 2, 4-6, 10, 11,13-16, and 18-21 from the 5′ end of the sense strand; (b) an antisensestrand consisting of 21 nucleotides, wherein nucleotides at positions 2and 14 from the 5′ end of the antisense strand are 2′-fluoronucleotides; and wherein nucleotides at positions 1, 3-13, and 15-21 are2′-O-methyl nucleotides. The ds-siNA may further comprise a conjugatedmoiety attached to the 3′ end of the sense strand. The ds-siNA mayfurther comprise (i) phosphorothioate internucleoside linkages betweenthe nucleotides at positions 1 and 2; positions 2 and 3; positions 19and 20; and positions 20 and 21 from the 5′ end of the sense strand; and(ii) phosphorothioate internucleoside linkages between the nucleotidesat positions 1 and 2; positions 2 and 3; positions 19 and 20; andpositions 20 and 21 from the 5′ end of the antisense strand. In someembodiments, the 2′-O-methyl nucleotide at position 1 from the 5′ end ofthe sense strand is further modified to contain a 5′ stabilizing endcap. In some embodiments, the 2′-O-methyl nucleotide at position 1 fromthe 5′ end of the antisense strand is further modified to contain a 5′stabilizing end cap. In some embodiments, the 2′-O-methyl nucleotide atposition 1 from the 5′ end of the sense strand is further modified tocontain a phosphorylation blocker. In some embodiments, the 2′-O-methylnucleotide at position 1 from the 3′ end of the sense strand is furthermodified to contain a phosphorylation blocker. In some embodiments, the2′-O-methyl nucleotide at position 1 from the 5′ end of the antisensestrand is further modified to contain a phosphorylation blocker. In someembodiments, the 2′-O-methyl nucleotide at position 1 from the 3′ end ofthe antisense strand is further modified to contain a phosphorylationblocker. In some embodiments, the 2′-O-methyl nucleotide at position 1from the 5′ end of the sense strand is a d2vd3 nucleotide. In someembodiments, the 2′-O-methyl nucleotide at position 1 from the 5′ end ofthe antisense strand is a d2vd3 nucleotide. In some embodiments, the2′-O-methyl nucleotide at position 1 from the 3′ end of the sense strandis a d2vd3 nucleotide. In some embodiments, the 2′-O-methyl nucleotideat position 1 from the 3′ end of the antisense strand is a d2vd3nucleotide. In some embodiments, at least 1, 2, 3, 4 or more 2′-fluoronucleotides on the sense strand or antisense strand is a 2′-fluoronucleotide mimic. In some embodiments, at least 1, 2, 3, 4 or more2′-fluoro nucleotides on the sense strand or antisense strand is a f4P,f2P, or fX nucleotide. In some embodiments, at least 1, 2, 3, 4 or more2′-O-methyl nucleotide on the sense or antisense strand is a 2′-O-methylnucleotide mimic.

As shown in FIG. 6B, a ds-siNA may comprise (a) a sense strandconsisting of 21 nucleotides, wherein 2′-fluoro nucleotides are atpositions 3, 7, 8, 12, and 17 from the 5′ end of the sense strand, andwherein 2′-O-methyl nucleotides are at positions 1, 2, 4-6, 9-11, 13-16,and 18-21 from the 5′ end of the sense strand; (b) an antisense strandconsisting of 21 nucleotides, wherein nucleotides at positions 2 and 14from the 5′ end of the antisense strand are 2′-fluoro nucleotides; andwherein nucleotides at positions 1, 3-13, and 15-21 are 2′-O-methylnucleotides. The ds-siNA may further comprise a conjugated moietyattached to the 3′ end of the sense strand. The ds-siNA may furthercomprise (i) phosphorothioate internucleoside linkages between thenucleotides at positions 1 and 2; positions 2 and 3; positions 19 and20; and positions 20 and 21 from the 5′ end of the sense strand; and(ii) phosphorothioate internucleoside linkages between the nucleotidesat positions 1 and 2; positions 2 and 3; positions 19 and 20; andpositions 20 and 21 from the 5′ end of the antisense strand. In someembodiments, the 2′-O-methyl nucleotide at position 1 from the 5′ end ofthe sense strand is further modified to contain a 5′ stabilizing endcap. In some embodiments, the 2′-O-methyl nucleotide at position 1 fromthe 5′ end of the antisense strand is further modified to contain a 5′stabilizing end cap. In some embodiments, the 2′-O-methyl nucleotide atposition 1 from the 5′ end of the sense strand is further modified tocontain a phosphorylation blocker. In some embodiments, the 2′-O-methylnucleotide at position 1 from the 3′ end of the sense strand is furthermodified to contain a phosphorylation blocker. In some embodiments, the2′-O-methyl nucleotide at position 1 from the 5′ end of the antisensestrand is further modified to contain a phosphorylation blocker. In someembodiments, the 2′-O-methyl nucleotide at position 1 from the 3′ end ofthe antisense strand is further modified to contain a phosphorylationblocker. In some embodiments, the 2′-O-methyl nucleotide at position 1from the 5′ end of the sense strand is a d2vd3 nucleotide. In someembodiments, the 2′-O-methyl nucleotide at position 1 from the 5′ end ofthe antisense strand is a d2vd3 nucleotide. In some embodiments, the2′-O-methyl nucleotide at position 1 from the 3′ end of the sense strandis a d2vd3 nucleotide. In some embodiments, the 2′-O-methyl nucleotideat position 1 from the 3′ end of the antisense strand is a d2vd3nucleotide. In some embodiments, at least 1, 2, 3, 4 or more 2′-fluoronucleotides on the sense strand or antisense strand is a 2′-fluoronucleotide mimic. In some embodiments, at least 1, 2, 3, 4 or more2′-fluoro nucleotides on the sense strand or antisense strand is a f4P,f2P, or fX nucleotide. In some embodiments, at least 1, 2, 3, 4 or more2′-O-methyl nucleotide on the sense or antisense strand is a 2′-O-methylnucleotide mimic.

As shown in FIG. 6C, a ds-siNA may comprise (a) a sense strandconsisting of 21 nucleotides, wherein 2′-fluoro nucleotides are atpositions 3, 7-9, 12, and 17 from the 5′ end of the sense strand, andwherein 2′-O-methyl nucleotides are at positions 1, 2, 4-6, 10, 11,13-16, and 18-21 from the 5′ end of the sense strand; (b) an antisensestrand consisting of 21 nucleotides, wherein the nucleotides in theantisense strand comprise an alternating 1:3 modification pattern, andwherein 1 nucleotide is a 2′-fluoro nucleotide and 3 nucleotides are2′-O-methyl nucleotides. The ds-siNA may further comprise a conjugatedmoiety attached to the 3′ end of the sense strand. The ds-siNA mayfurther comprise (i) phosphorothioate internucleoside linkages betweenthe nucleotides at positions 1 and 2; and positions 2 and 3; positions19 and 20; and positions 20 and 21 from the 5′ end of the sense strand;and (ii) phosphorothioate internucleoside linkages between thenucleotides at positions 1 and 2; positions 2 and 3; positions 19 and20; and positions 20 and 21 from the 5′ end of the antisense strand. Theds-siNA may comprise 2-5 alternating 1:3 modification patterns on theantisense strand. In some embodiments, the 2′-O-methyl nucleotide atposition 1 from the 5′ end of the sense strand is further modified tocontain a 5′ stabilizing end cap. In some embodiments, the 2′-O-methylnucleotide at position 1 from the 5′ end of the antisense strand isfurther modified to contain a 5′ stabilizing end cap. In someembodiments, the 2′-O-methyl nucleotide at position 1 from the 5′ end ofthe sense strand is further modified to contain a phosphorylationblocker. In some embodiments, the 2′-O-methyl nucleotide at position 1from the 3′ end of the sense strand is further modified to contain aphosphorylation blocker. In some embodiments, the 2′-O-methyl nucleotideat position 1 from the 5′ end of the antisense strand is furthermodified to contain a phosphorylation blocker. In some embodiments, the2′-O-methyl nucleotide at position 1 from the 3′ end of the antisensestrand is further modified to contain a phosphorylation blocker. In someembodiments, the 2′-O-methyl nucleotide at position 1 from the 5′ end ofthe sense strand is a d2vd3 nucleotide. In some embodiments, the2′-O-methyl nucleotide at position 1 from the 5′ end of the antisensestrand is a d2vd3 nucleotide. In some embodiments, the 2′-O-methylnucleotide at position 1 from the 3′ end of the sense strand is a d2vd3nucleotide. In some embodiments, the 2′-O-methyl nucleotide at position1 from the 3′ end of the antisense strand is a d2vd3 nucleotide. In someembodiments, at least 1, 2, 3, 4 or more 2′-fluoro nucleotides on thesense strand or antisense strand is a 2′-fluoro nucleotide mimic. Insome embodiments, at least 1, 2, 3, 4 or more 2′-fluoro nucleotides onthe sense strand is a f4P, f2P, or fX nucleotide. In some embodiments,at least 1, 2, 3, 4 or more 2′-fluoro nucleotides on the antisensestrand is a f4P, f2P, or fX nucleotide. In some embodiments, at least 1,2, 3, 4 or more 2′-O-methyl nucleotide on the sense or antisense strandis a 2′-O-methyl nucleotide mimic.

As shown in FIG. 6D, a ds-siNA may comprise (a) a sense strandconsisting of 21 nucleotides, wherein 2′-fluoro nucleotides are atpositions 5 and 7-9 from the 5′ end of the sense strand, and wherein2′-O-methyl nucleotides are at positions 1-4, 6, and 10-21 from the 5′end of the sense strand; (b) an antisense strand consisting of 21nucleotides, wherein the nucleotides in the antisense strand comprise analternating 1:3 modification pattern, and wherein 1 nucleotide is a2′-fluoro nucleotide and 3 nucleotides are 2′-O-methyl nucleotides. Theds-siNA may further comprise a conjugated moiety attached to the 3′ endof the sense strand. The ds-siNA may further comprise (i)phosphorothioate internucleoside linkages between the nucleotides atpositions 1 and 2; positions 2 and 3; positions 19 and 20; and positions20 and 21 from the 5′ end of the sense strand; and (ii) phosphorothioateinternucleoside linkages between the nucleotides at positions 1 and 2;positions 2 and 3; positions 19 and 20; and positions 20 and 21 from the5′ end of the antisense strand. The ds-siNA may comprise 2-5 alternating1:3 modification patterns on the antisense strand. The alternating 1:3modification pattern may start at the nucleotide at any of positions 2,6, 10, 14, and/or 18 from the 5′ end of the antisense strand. In someembodiments, the 2′-O-methyl nucleotide at position 1 from the 5′ end ofthe sense strand is further modified to contain a 5′ stabilizing endcap. In some embodiments, the 2′-O-methyl nucleotide at position 1 fromthe 5′ end of the antisense strand is further modified to contain a 5′stabilizing end cap. In some embodiments, the 2′-O-methyl nucleotide atposition 1 from the 5′ end of the sense strand is further modified tocontain a phosphorylation blocker. In some embodiments, the 2′-O-methylnucleotide at position 1 from the 3′ end of the sense strand is furthermodified to contain a phosphorylation blocker. In some embodiments, the2′-O-methyl nucleotide at position 1 from the 5′ end of the antisensestrand is further modified to contain a phosphorylation blocker. In someembodiments, the 2′-O-methyl nucleotide at position 1 from the 3′ end ofthe antisense strand is further modified to contain a phosphorylationblocker. In some embodiments, the 2′-O-methyl nucleotide at position 1from the 5′ end of the sense strand is a d2vd3 nucleotide. In someembodiments, the 2′-O-methyl nucleotide at position 1 from the 5′ end ofthe antisense strand is a d2vd3 nucleotide. In some embodiments, the2′-O-methyl nucleotide at position 1 from the 3′ end of the sense strandis a d2vd3 nucleotide. In some embodiments, the 2′-O-methyl nucleotideat position 1 from the 3′ end of the antisense strand is a d2vd3nucleotide. In some embodiments, at least 1, 2, 3, 4 or more 2′-fluoronucleotides on the sense strand or antisense strand is a 2′-fluoronucleotide mimic. In some embodiments, at least 1, 2, 3, 4 or more2′-fluoro nucleotides on the sense strand is a f4P, f2P, or fXnucleotide. In some embodiments, at least 1, 2, 3, 4 or more 2′-fluoronucleotides on the antisense strand is a f4P, f2P, or fX nucleotide. Insome embodiments, at least 1, 2, 3, 4 or more 2′-O-methyl nucleotide onthe sense or antisense strand is a 2′-O-methyl nucleotide mimic.

As shown in FIG. 6E, a ds-siNA may comprise (a) a sense strandconsisting of 21 nucleotides, wherein 2′-fluoro nucleotides are atpositions 5 and 7-9 from the 5′ end of the sense strand, and wherein2′-O-methyl nucleotides are at positions 1-4, 6, and 10-21 from the 5′end of the sense strand; (b) an antisense strand consisting of 21nucleotides, wherein nucleotides at positions 2, 5, 8, 14, and 17 fromthe 5′ end of the antisense strand are 2′-fluoro nucleotides; andwherein nucleotides at positions 1, 3-13, and 15-21 are 2′-O-methylnucleotides. The ds-siNA may further comprise a conjugated moietyattached to the 3′ end of the sense strand. The ds-siNA may furthercomprise (i) phosphorothioate internucleoside linkages between thenucleotides at positions 1 and 2; positions 2 and 3; positions 19 and20; and positions 20 and 21 from the 5′ end of the sense strand; and(ii) phosphorothioate internucleoside linkages between the nucleotidesat positions 1 and 2; positions 2 and 3; positions 19 and 20; andpositions 20 and 21 from the 5′ end of the antisense strand. The ds-siNAmay comprise 2-5 alternating 1:2 modification patterns on the antisensestrand. The alternating 1:2 modification pattern may start at thenucleotide at any of positions 2, 5, 8, 14, and/or 17 from the 5′ end ofthe antisense strand. In some embodiments, the ds-siNA comprises (a) asense strand consisting of 19 nucleotides, wherein 2′-fluoro nucleotidesare at positions 5 and 7-9 from the 5′ end of the sense strand, andwherein 2′-O-methyl nucleotides are at positions 1-4, 6, and 10-19 fromthe 5′ end of the sense strand; (b) an antisense strand consisting of 21nucleotides, wherein 2′-fluoro nucleotides are at positions 2, 5, 8, 14,and 17 from the 5′ end of the antisense strand, and wherein 2′-O-methylnucleotides are at positions 1, 3, 4, 6, 7, 9-13, 15, 16, and 18-21 fromthe 5′ end of the sense strand. In some embodiments, the 2′-O-methylnucleotide at position 1 from the 5′ end of the sense strand is furthermodified to contain a 5′ stabilizing end cap. In some embodiments, the2′-O-methyl nucleotide at position 1 from the 5′ end of the antisensestrand is further modified to contain a 5′ stabilizing end cap. In someembodiments, the 2′-O-methyl nucleotide at position 1 from the 5′ end ofthe sense strand is further modified to contain a phosphorylationblocker. In some embodiments, the 2′-O-methyl nucleotide at position 1from the 3′ end of the sense strand is further modified to contain aphosphorylation blocker. In some embodiments, the 2′-O-methyl nucleotideat position 1 from the 5′ end of the antisense strand is furthermodified to contain a phosphorylation blocker. In some embodiments, the2′-O-methyl nucleotide at position 1 from the 3′ end of the antisensestrand is further modified to contain a phosphorylation blocker. In someembodiments, the 2′-O-methyl nucleotide at position 1 from the 5′ end ofthe sense strand is a d2vd3 nucleotide. In some embodiments, the2′-O-methyl nucleotide at position 1 from the 5′ end of the antisensestrand is a d2vd3 nucleotide. In some embodiments, the 2′-O-methylnucleotide at position 1 from the 3′ end of the sense strand is a d2vd3nucleotide. In some embodiments, the 2′-O-methyl nucleotide at position1 from the 3′ end of the antisense strand is a d2vd3 nucleotide. In someembodiments, at least 1, 2, 3, 4 or more 2′-fluoro nucleotides on thesense strand or antisense strand is a 2′-fluoro nucleotide mimic. Insome embodiments, at least 1, 2, 3, 4 or more 2′-fluoro nucleotides onthe sense strand is a f4P, f2P, or fX nucleotide. In some embodiments,at least 1, 2, 3, 4 or more 2′-fluoro nucleotides on the antisensestrand is a f4P, f2P, or fX nucleotide. In some embodiments, at least 1,2, 3, 4 or more 2′-O-methyl nucleotide on the sense or antisense strandis a 2′-O-methyl nucleotide mimic.

As shown in FIG. 6F, a ds-siNA may comprise (a) a sense strandconsisting of 21 nucleotides, wherein 2′-fluoro nucleotides are atpositions 5 and 7-9 from the 5′ end of the sense strand, and wherein2′-O-methyl nucleotides are at positions 1-4, 6, and 10-21 from the 5′end of the sense strand; (b) an antisense strand consisting of 21nucleotides, wherein 2′-fluoro nucleotides are at positions 2, 6, 14,and 16 from the 5′ end of the antisense strand, and wherein 2′-O-methylnucleotides are at positions 1, 3-5, 7-13, 15, and 17-21 from the 5′ endof the antisense strand. The ds-siNA may further comprise a conjugatedmoiety attached to the 3′ end of the sense strand. The ds-siNA mayfurther comprise (i) phosphorothioate internucleoside linkages betweenthe nucleotides at positions 1 and 2; positions 2 and 3; positions 19and 20; and positions 20 and 21 from the 5′ end of the sense strand; and(ii) phosphorothioate internucleoside linkages between the nucleotidesat positions 1 and 2; positions 2 and 3; positions 19 and 20; andpositions 20 and 21 from the 5′ end of the antisense strand. In someembodiments, at least 1, 2, 3, 4 or more 2′-fluoro nucleotides on thesense strand or antisense strand is a f4P, f2P, or fX nucleotide. Insome embodiments, at least 1, 2, 3, 4 or more 2′-fluoro nucleotides onthe sense strand or antisense strand is a f4P nucleotide. In someembodiments, at least 1, 2, 3, or 4 of the 2′-fluoro-nucleotides atpositions 2, 6, 14, and 16 from the 5′ end of the antisense strand is af4P nucleotide. In some embodiments, at least one of the2′-fluoro-nucleotides at positions 2, 6, 14, and 16 from the 5′ end ofthe antisense strand is a f4P nucleotide. In some embodiments, at leasttwo of the 2′-fluoro-nucleotides at positions 2, 6, 14, and 16 from the5′ end of the antisense strand is a f4P nucleotide. In some embodiments,less than or equal to 3 of the 2′-fluoro-nucleotides at positions 2, 6,14, and 16 from the 5′ end of the antisense strand is a f4P nucleotide.In some embodiments, less than or equal to 2 of the2′-fluoro-nucleotides at positions 2, 6, 14, and 16 from the 5′ end ofthe antisense strand is a f4P nucleotide. In some embodiments, the2′-fluoro-nucleotide at position 2 from the 5′ end of the antisensestrand is a f4P nucleotide. In some embodiments, the2′-fluoro-nucleotide at position 6 from the 5′ end of the antisensestrand is a f4P nucleotide. In some embodiments, the2′-fluoro-nucleotide at position 14 from the 5′ end of the antisensestrand is a f4P nucleotide. In some embodiments, the2′-fluoro-nucleotide at position 16 from the 5′ end of the antisensestrand is a f4P nucleotide. In some embodiments, at least 1, 2, 3, 4 ormore 2′-fluoro nucleotides on the sense strand or antisense strand is af2P nucleotide. In some embodiments, at least 1, 2, 3, or 4 of the2′-fluoro-nucleotides at positions 2, 6, 14, and 16 from the 5′ end ofthe antisense strand is a f2P nucleotide. In some embodiments, at leastone of the 2′-fluoro-nucleotides at positions 2, 6, 14, and 16 from the5′ end of the antisense strand is a f2P nucleotide. In some embodiments,at least two of the 2′-fluoro-nucleotides at positions 2, 6, 14, and 16from the 5′ end of the antisense strand is a f2P nucleotide. In someembodiments, less than or equal to 3 of the 2′-fluoro-nucleotides atpositions 2, 6, 14, and 16 from the 5′ end of the antisense strand is af2P nucleotide. In some embodiments, less than or equal to 2 of the2′-fluoro-nucleotides at positions 2, 6, 14, and 16 from the 5′ end ofthe antisense strand is a f2P nucleotide. In some embodiments, the2′-fluoro-nucleotide at position 2 from the 5′ end of the antisensestrand is a f2P nucleotide. In some embodiments, the2′-fluoro-nucleotide at position 6 from the 5′ end of the antisensestrand is a f2P nucleotide. In some embodiments, the2′-fluoro-nucleotide at position 14 from the 5′ end of the antisensestrand is a f2P nucleotide. In some embodiments, the2′-fluoro-nucleotide at position 16 from the 5′ end of the antisensestrand is a f2P nucleotide. In some embodiments, at least 1, 2, 3, 4 ormore 2′-fluoro nucleotides on the sense strand or antisense strand is afX nucleotide. In some embodiments, at least 1, 2, 3, or 4 of the2′-fluoro-nucleotides at positions 2, 6, 14, and 16 from the 5′ end ofthe antisense strand is a fX nucleotide. In some embodiments, at leastone of the 2′-fluoro-nucleotides at positions 2, 6, 14, and 16 from the5′ end of the antisense strand is a fX nucleotide. In some embodiments,at least two of the 2′-fluoro-nucleotides at positions 2, 6, 14, and 16from the 5′ end of the antisense strand is a fX nucleotide. In someembodiments, less than or equal to 3 of the 2′-fluoro-nucleotides atpositions 2, 6, 14, and 16 from the 5′ end of the antisense strand is afX nucleotide. In some embodiments, less than or equal to 2 of the2′-fluoro-nucleotides at positions 2, 6, 14, and 16 from the 5′ end ofthe antisense strand is a fX nucleotide. In some embodiments, the2′-fluoro-nucleotide at position 2 from the 5′ end of the antisensestrand is a fX nucleotide. In some embodiments, the 2′-fluoro-nucleotideat position 6 from the 5′ end of the antisense strand is a fXnucleotide. In some embodiments, the 2′-fluoro-nucleotide at position 14from the 5′ end of the antisense strand is a fX nucleotide. In someembodiments, the 2′-fluoro-nucleotide at position 16 from the 5′ end ofthe antisense strand is a fX nucleotide. In some embodiments, the2′-O-methyl nucleotide at position 1 from the 5′ end of the sense strandis further modified to contain a 5′ stabilizing end cap. In someembodiments, the 2′-O-methyl nucleotide at position 1 from the 5′ end ofthe antisense strand is further modified to contain a 5′ stabilizing endcap. In some embodiments, the 2′-O-methyl nucleotide at position 1 fromthe 5′ end of the sense strand is further modified to contain aphosphorylation blocker. In some embodiments, the 2′-O-methyl nucleotideat position 1 from the 3′ end of the sense strand is further modified tocontain a phosphorylation blocker. In some embodiments, the 2′-O-methylnucleotide at position 1 from the 5′ end of the antisense strand isfurther modified to contain a phosphorylation blocker. In someembodiments, the 2′-O-methyl nucleotide at position 1 from the 3′ end ofthe antisense strand is further modified to contain a phosphorylationblocker. In some embodiments, the 2′-O-methyl nucleotide at position 1from the 5′ end of the sense strand is a d2vd3 nucleotide. In someembodiments, the 2′-O-methyl nucleotide at position 1 from the 5′ end ofthe antisense strand is a d2vd3 nucleotide. In some embodiments, the2′-O-methyl nucleotide at position 1 from the 3′ end of the sense strandis a d2vd3 nucleotide. In some embodiments, the 2′-O-methyl nucleotideat position 1 from the 3′ end of the antisense strand is a d2vd3nucleotide. In some embodiments, at least 1, 2, 3, 4 or more 2′-fluoronucleotides on the sense strand or antisense strand is a 2′-fluoronucleotide mimic. In some embodiments, at least 1, 2, 3, 4 or more2′-fluoro nucleotides on the sense strand is a f4P, f2P, or fXnucleotide. In some embodiments, at least 1, 2, 3, 4 or more 2′-fluoronucleotides on the antisense strand is a f4P, f2P, or fX nucleotide. Insome embodiments, at least 1, 2, 3, 4 or more 2′-O-methyl nucleotide onthe sense or antisense strand is a 2′-O-methyl nucleotide mimic.

As shown in FIG. 6G, a ds-siNA may comprise (a) a sense strandconsisting of 21 nucleotides, wherein 2′-fluoro nucleotides are atpositions 5, 9-11, 14, and 19 from the 5′ end of the sense strand, andwherein 2′-O-methyl nucleotides are at positions 1-4, 6-8, 12, 13,15-18, 20, and 21 from the 5′ end of the sense strand; and (b) anantisense strand consisting of 23 nucleotides, wherein 2′-flouronucleotides are at positions 2 and 14 from the 5′ end of the antisensestrand, and wherein 2′-O-methyl nucleotides are at positions 1, 3-13,and 15-23 from the 5′ end of the antisense strand. The ds-siNA mayfurther comprise a conjugated moiety attached to the 3′ end of the sensestrand. The ds-siNA may further comprise (i) phosphorothioateinternucleoside linkages between the nucleotides at positions 1 and 2;positions 2 and 3; and positions 20 and 21 from the 5′ end of the sensestrand; and (ii) phosphorothioate internucleoside linkages between thenucleotides at positions 1 and 2; positions 2 and 3; positions 21 and22; and positions 22 and 23 from the 5′ end of the antisense strand. Insome embodiments, the 2′-O-methyl nucleotide at position 1 from the 5′end of the sense strand is further modified to contain a 5′ stabilizingend cap. In some embodiments, the 2′-O-methyl nucleotide at position 1from the 5′ end of the antisense strand is further modified to contain a5′ stabilizing end cap. In some embodiments, the 2′-O-methyl nucleotideat position 1 from the 5′ end of the sense strand is further modified tocontain a phosphorylation blocker. In some embodiments, the 2′-O-methylnucleotide at position 1 from the 3′ end of the sense strand is furthermodified to contain a phosphorylation blocker. In some embodiments, the2′-O-methyl nucleotide at position 1 from the 5′ end of the antisensestrand is further modified to contain a phosphorylation blocker. In someembodiments, the 2′-O-methyl nucleotide at position 1 from the 3′ end ofthe antisense strand is further modified to contain a phosphorylationblocker. In some embodiments, the 2′-O-methyl nucleotide at position 1from the 5′ end of the sense strand is a d2vd3 nucleotide. In someembodiments, the 2′-O-methyl nucleotide at position 1 from the 5′ end ofthe antisense strand is a d2vd3 nucleotide. In some embodiments, the2′-O-methyl nucleotide at position 1 from the 3′ end of the sense strandis a d2vd3 nucleotide. In some embodiments, the 2′-O-methyl nucleotideat position 1 from the 3′ end of the antisense strand is a d2vd3nucleotide. In some embodiments, at least 1, 2, 3, 4 or more 2′-fluoronucleotides on the sense strand or antisense strand is a 2′-fluoronucleotide mimic. In some embodiments, at least 1, 2, 3, 4 or more2′-fluoro nucleotides on the sense strand is a f4P, f2P, or fXnucleotide. In some embodiments, at least 1, 2, 3, 4 or more 2′-fluoronucleotides on the antisense strand is a f4P, f2P, or fX nucleotide. Insome embodiments, at least 1, 2, 3, 4 or more 2′-O-methyl nucleotide onthe sense or antisense strand is a 2′-O-methyl nucleotide mimic.

As shown in FIG. 6H, a ds-siNA may comprise (a) a sense strandconsisting of 21 nucleotides, wherein 2′-fluoro nucleotides are atpositions 7 and 9-11 from the 5′ end of the sense strand, and wherein2′-O-methyl nucleotides are at positions 1-6, 8, and 12-21 from the 5′end of the sense strand; and (b) an antisense strand consisting of 23nucleotides, wherein 2′-flouro nucleotides are at positions 2, 6, 14,and 16 from the 5′ end of the antisense strand, and wherein 2′-O-methylnucleotides are at positions 1, 3-5, 7-13, 15, and 17-23 from the 5′ endof the antisense strand. The ds-siNA may further comprise a conjugatedmoiety attached to the 3′ end of the sense strand. The ds-siNA mayfurther comprise (i) phosphorothioate internucleoside linkages betweenthe nucleotides at positions 1 and 2; positions 2 and 3; and positions20 and 21 from the 5′ end of the sense strand; and (ii) phosphorothioateinternucleoside linkages between the nucleotides at positions 1 and 2;positions 2 and 3; positions 21 and 22; and positions 22 and 23 from the5′ end of the antisense strand. In some embodiments, the 2′-O-methylnucleotide at position 1 from the 5′ end of the sense strand is furthermodified to contain a 5′ stabilizing end cap. In some embodiments, the2′-O-methyl nucleotide at position 1 from the 5′ end of the antisensestrand is further modified to contain a 5′ stabilizing end cap. In someembodiments, the 2′-O-methyl nucleotide at position 1 from the 5′ end ofthe sense strand is further modified to contain a phosphorylationblocker. In some embodiments, the 2′-O-methyl nucleotide at position 1from the 3′ end of the sense strand is further modified to contain aphosphorylation blocker. In some embodiments, the 2′-O-methyl nucleotideat position 1 from the 5′ end of the antisense strand is furthermodified to contain a phosphorylation blocker. In some embodiments, the2′-O-methyl nucleotide at position 1 from the 3′ end of the antisensestrand is further modified to contain a phosphorylation blocker. In someembodiments, the 2′-O-methyl nucleotide at position 1 from the 5′ end ofthe sense strand is a d2vd3 nucleotide. In some embodiments, the2′-O-methyl nucleotide at position 1 from the 5′ end of the antisensestrand is a d2vd3 nucleotide. In some embodiments, the 2′-O-methylnucleotide at position 1 from the 3′ end of the sense strand is a d2vd3nucleotide. In some embodiments, the 2′-O-methyl nucleotide at position1 from the 3′ end of the antisense strand is a d2vd3 nucleotide. In someembodiments, at least 1, 2, 3, 4 or more 2′-fluoro nucleotides on thesense strand or antisense strand is a 2′-fluoro nucleotide mimic. Insome embodiments, at least 1, 2, 3, 4 or more 2′-fluoro nucleotides onthe sense strand is a f4P, f2P, or fX nucleotide. In some embodiments,at least 1, 2, 3, 4 or more 2′-fluoro nucleotides on the antisensestrand is a f4P, f2P, or fX nucleotide. In some embodiments, at least 1,2, 3, 4 or more 2′-O-methyl nucleotide on the sense or antisense strandis a 2′-O-methyl nucleotide mimic.

As shown in FIG. 6I, a ds-siNA may comprise (a) a sense strandconsisting of 21 nucleotides, wherein 2′-fluoro nucleotides are atpositions 7 and 9-11 from the 5′ end of the sense strand, and wherein2′-O-methyl nucleotides are at positions 1-6, 8, and 12-21 from the 5′end of the sense strand; and (b) an antisense strand consisting of 23nucleotides, wherein 2′-flouro nucleotides are at positions 2, 5, 8, 14,17, and 20 from the 5′ end of the antisense strand, and wherein2′-O-methyl nucleotides are at positions 1, 3, 4, 6, 9-13, 15, 16, 18,19, and 21-23 from the 5′ end of the antisense strand. The ds-siNA mayfurther comprise a conjugated moiety attached to the 3′ end of the sensestrand. The ds-siNA may further comprise (i) phosphorothioateinternucleoside linkages between the nucleotides at positions 1 and 2;positions 2 and 3; and positions 20 and 21 from the 5′ end of the sensestrand; and (ii) phosphorothioate internucleoside linkages between thenucleotides at positions 1 and 2; positions 2 and 3; positions 21 and22; and positions 22 and 23 from the 5′ end of the antisense strand. Insome embodiments, the 2′-O-methyl nucleotide at position 1 from the 5′end of the sense strand is further modified to contain a 5′ stabilizingend cap. In some embodiments, the 2′-O-methyl nucleotide at position 1from the 5′ end of the antisense strand is further modified to contain a5′ stabilizing end cap. In some embodiments, the 2′-O-methyl nucleotideat position 1 from the 5′ end of the sense strand is further modified tocontain a phosphorylation blocker. In some embodiments, the 2′-O-methylnucleotide at position 1 from the 3′ end of the sense strand is furthermodified to contain a phosphorylation blocker. In some embodiments, the2′-O-methyl nucleotide at position 1 from the 5′ end of the antisensestrand is further modified to contain a phosphorylation blocker. In someembodiments, the 2′-O-methyl nucleotide at position 1 from the 3′ end ofthe antisense strand is further modified to contain a phosphorylationblocker. In some embodiments, the 2′-O-methyl nucleotide at position 1from the 5′ end of the sense strand is a d2vd3 nucleotide. In someembodiments, the 2′-O-methyl nucleotide at position 1 from the 5′ end ofthe antisense strand is a d2vd3 nucleotide. In some embodiments, the2′-O-methyl nucleotide at position 1 from the 3′ end of the sense strandis a d2vd3 nucleotide. In some embodiments, the 2′-O-methyl nucleotideat position 1 from the 3′ end of the antisense strand is a d2vd3nucleotide. In some embodiments, at least 1, 2, 3, 4 or more 2′-fluoronucleotides on the sense strand or antisense strand is a 2′-fluoronucleotide mimic. In some embodiments, at least 1, 2, 3, 4 or more2′-fluoro nucleotides on the sense strand is a f4P, f2P, or fXnucleotide. In some embodiments, at least 1, 2, 3, 4 or more 2′-fluoronucleotides on the antisense strand is a f4P, f2P, or fX nucleotide. Insome embodiments, at least 1, 2, 3, 4 or more 2′-O-methyl nucleotide onthe sense or antisense strand is a 2′-O-methyl nucleotide mimic.

In some embodiments, the nucleotides in the antisense strand maycomprise an alternating 1:2 modification pattern, wherein 1 nucleotideis a 2′-fluoro nucleotide and 2 nucleotides are 2′-O-methyl nucleotides.In some embodiments, the nucleotides in the antisense strand maycomprise an alternating 1:1 modification pattern (i.e., an alternatingpattern), wherein 1 nucleotide is a 2′-fluoro nucleotide and 1nucleotide is a 2′-O-methyl nucleotide in an alternating fashion. Thesealternating modification patterns may start at any nucleotide of theantisense strand.

Any of the siNAs disclosed herein may comprise a sense strand and anantisense strand. The sense strand may comprise a first nucleotidesequence that is 15 to 30 nucleotides in length. The antisense strandmay comprise a second nucleotide sequence that is 15 to 30 nucleotidesin length.

A double-stranded short interfering nucleic acid (ds-siNA) molecule ofthis disclosure may comprise: (a) a sense strand comprising a firstnucleotide sequence that is at least about 60%, 65%, 70%, 75%, 80%, 85%,90%, 95%, or 100% identical to an RNA corresponding to a target gene,wherein the first nucleotide sequence: (i) is 15 to 30 nucleotides inlength; and (ii) comprises 15 or more modified nucleotides independentlyselected from a 2′-O-methyl nucleotide and a 2′-fluoro nucleotide,wherein at least one modified nucleotide is a 2′-O-methyl nucleotide andthe nucleotide at position 3, 5, 7, 8, 9, 10, 11, 12, 14, 17, and/or 19from the 5′ end of the first nucleotide sequence is a 2′-fluoronucleotide; and (b) an antisense strand comprising a second nucleotidesequence that is at least about 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%,or 100% complementary to the RNA corresponding to the target gene,wherein the second nucleotide sequence: (i) is 15 to 30 nucleotides inlength; and (ii) comprises 15 or more modified nucleotides independentlyselected from a 2′-O-methyl nucleotide and a 2′-fluoro nucleotide,wherein at least one modified nucleotide is a 2′-O-methyl nucleotide andat least one modified nucleotide is a 2′-fluoro nucleotide.

A double-stranded short interfering nucleic acid (ds-siNA) molecule ofthe disclosure may comprise: (a) a sense strand comprising a firstnucleotide sequence that is at least about 60%, 65%, 70%, 75%, 80%, 85%,90%, 95%, or 100% identical to an RNA corresponding to a target gene,wherein the first nucleotide sequence: (i) is 15 to 30 nucleotides inlength; and (ii) comprises 15 or more modified nucleotides independentlyselected from a 2′-O-methyl nucleotide and a 2′-fluoro nucleotide,wherein at least one modified nucleotide is a 2′-O-methyl nucleotide andthe nucleotide at position 3, 5, 7, 8, 9, 10, 11, 12, 14, 17, and/or 19from the 5′ end of the first nucleotide sequence is a 2′-fluoronucleotide; and (b) an antisense strand comprising a second nucleotidesequence that is at least about 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%,or 100% complementary to the RNA corresponding to the target gene,wherein the second nucleotide sequence: (i) is 15 to 30 nucleotides inlength; and (ii) comprises 15 or more modified nucleotides independentlyselected from a 2′-O-methyl nucleotide and a 2′-fluoro nucleotide,wherein at least one modified nucleotide is a 2′-O-methyl nucleotide andat least one modified nucleotide is a 2′-fluoro nucleotide.

A double-stranded short interfering nucleic acid (ds-siNA) molecule ofthe disclosure may comprise: (a) a sense strand comprising a firstnucleotide sequence that is at least about 60%, 65%, 70%, 75%, 80%, 85%,90%, 95%, or 100% identical to an RNA corresponding to a target gene,wherein the first nucleotide sequence: (i) is 15 to 30 nucleotides inlength; and (ii) comprises 15 or more modified nucleotides independentlyselected from a 2′-O-methyl nucleotide and a 2′-fluoro nucleotide,wherein at least one modified nucleotide is a 2′-O-methyl nucleotide andthe nucleotide at position 7 from the 5′ end of the first nucleotidesequence is a 2′-fluoro nucleotide; and (b) an antisense strandcomprising a second nucleotide sequence that is at least about 60%, 65%,70%, 75%, 80%, 85%, 90%, 95%, or 100% complementary to the RNAcorresponding to the target gene, wherein the second nucleotidesequence: (i) is 15 to 30 nucleotides in length; and (ii) comprises 15or more modified nucleotides independently selected from a 2′-O-methylnucleotide and a 2′-fluoro nucleotide, wherein at least one modifiednucleotide is a 2′-O-methyl nucleotide and at least one modifiednucleotide is a 2′-fluoro nucleotide.

A double-stranded short interfering nucleic acid (ds-siNA) molecule ofthe disclosure may comprise: (a) a sense strand comprising a firstnucleotide sequence that is at least about 60%, 65%, 70%, 75%, 80%, 85%,90%, 95%, or 100% identical to an RNA corresponding to a target gene,wherein the first nucleotide sequence: (i) is 15 to 30 nucleotides inlength; and (ii) comprises 15 or more modified nucleotides independentlyselected from a 2′-O-methyl nucleotide and a 2′-fluoro nucleotide,wherein at least one modified nucleotide is a 2′-O-methyl nucleotide andthe nucleotide at position 7, 9, 10, and/or 11 from the 5′ end of thefirst nucleotide sequence is a 2′-fluoro nucleotide; and (b) anantisense strand comprising a second nucleotide sequence that is atleast about 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, or 100%complementary to the RNA corresponding to the target gene, wherein thesecond nucleotide sequence: (i) is 15 to 30 nucleotides in length; and(ii) comprises 15 or more modified nucleotides independently selectedfrom a 2′-O-methyl nucleotide and a 2′-fluoro nucleotide, wherein atleast one modified nucleotide is a 2′-O-methyl nucleotide and at leastone modified nucleotide is a 2′-fluoro nucleotide.

A double-stranded short interfering nucleic acid (ds-siNA) molecule ofthe disclosure may comprise: (a) a sense strand comprising a firstnucleotide sequence that is at least about 60%, 65%, 70%, 75%, 80%, 85%,90%, 95%, or 100% identical to an RNA corresponding to a target gene,wherein the first nucleotide sequence: (i) is 15 to 30 nucleotides inlength; and (ii) comprises 15 or more modified nucleotides independentlyselected from a 2′-O-methyl nucleotide and a 2′-fluoro nucleotide,wherein at least one modified nucleotide is a 2′-O-methyl nucleotide andat least one modified nucleotide is a 2′-fluoro nucleotide; and (b) anantisense strand comprising a second nucleotide sequence that is atleast about 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, or 100%complementary to the RNA corresponding to the target gene, wherein thesecond nucleotide sequence: (i) is 15 to 30 nucleotides in length; and(ii) comprises 15 or more modified nucleotides independently selectedfrom a 2′-O-methyl nucleotide and a 2′-fluoro nucleotide, wherein atleast one modified nucleotide is a 2′-O-methyl nucleotide and thenucleotide at position 2, 5, 6, 8, 10, 14, 16, 17, and/or 18 from the 5′end of the second nucleotide sequence is a 2′-fluoro nucleotide.

A double-stranded short interfering nucleic acid (ds-siNA) molecule ofthe disclosure may comprise: (a) a sense strand comprising a firstnucleotide sequence that is at least about 60%, 65%, 70%, 75%, 80%, 85%,90%, 95%, or 100% identical to an RNA corresponding to a target gene,wherein the first nucleotide sequence: (i) is 15 to 30 nucleotides inlength; and (ii) comprises 15 or more modified nucleotides independentlyselected from a 2′-O-methyl nucleotide and a 2′-fluoro nucleotide,wherein at least one modified nucleotide is a 2′-O-methyl nucleotide andat least one modified nucleotide is a 2′-fluoro nucleotide; and (b) anantisense strand comprising a second nucleotide sequence that is atleast about 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, or 100%complementary to the RNA corresponding to the target gene, wherein thesecond nucleotide sequence: (i) is 15 to 30 nucleotides in length; and(ii) comprises 15 or more modified nucleotides independently selectedfrom a 2′-O-methyl nucleotide and a 2′-fluoro nucleotide, wherein atleast one modified nucleotide is a 2′-O-methyl nucleotide and thenucleotide at position 2 of the second nucleotide sequence is a2′-fluoro nucleotide.

A double-stranded short interfering nucleic acid (ds-siNA) molecule ofthe disclosure may comprise: (a) a sense strand comprising a firstnucleotide sequence that is at least about 60%, 65%, 70%, 75%, 80%, 85%,90%, 95%, or 100% identical to an RNA corresponding to a target gene,wherein the first nucleotide sequence: (i) is 15 to 30 nucleotides inlength; (ii) comprises 15 or more modified nucleotides independentlyselected from a 2′-O-methyl nucleotide and a 2′-fluoro nucleotide,wherein at least one modified nucleotide is a 2′-O-methyl nucleotide andat least one modified nucleotide is a 2′-fluoro nucleotide; and (iii)comprises 1 or more phosphorothioate internucleoside linkage; and (b) anantisense strand comprising a second nucleotide sequence that is atleast about 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, or 100%complementary to the RNA corresponding to the target gene, wherein thesecond nucleotide sequence: (i) is 15 to 30 nucleotides in length; (ii)comprises 15 or more modified nucleotides independently selected from a2′-O-methyl nucleotide and a 2′-fluoro nucleotide, wherein at least onemodified nucleotide is a 2′-O-methyl nucleotide and at least onemodified nucleotide is a 2′-fluoro nucleotide; and (iii) comprises 1 ormore phosphorothioate internucleoside linkage.

A double-stranded short interfering nucleic acid (ds-siNA) molecule ofthe disclosure may comprise: (a) a sense strand comprising a firstnucleotide sequence that is at least about 60%, 65%, 70%, 75%, 80%, 85%,90%, 95%, or 100% identical to an RNA corresponding to a target gene,wherein the first nucleotide sequence: (i) is 15 to 30 nucleotides inlength; and (ii) comprises 15 or more modified nucleotides independentlyselected from a 2′-O-methyl nucleotide and a 2′-fluoro nucleotide,wherein at least one modified nucleotide is a 2′-O-methyl nucleotide andat least one modified nucleotide is a 2′-fluoro nucleotide; and (b) anantisense strand comprising a second nucleotide sequence that is atleast about 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, or 100%complementary to the RNA corresponding to the target gene, wherein thesecond nucleotide sequence: (i) is 15 to 30 nucleotides in length; and(ii) comprises 15 or more modified nucleotides independently selectedfrom a 2′-O-methyl nucleotide and a 2′-fluoro nucleotide, wherein atleast one modified nucleotide is a 2′-O-methyl nucleotide and at leastone modified nucleotide is a 2′-fluoro nucleotide, wherein the ds-siNAmay further comprise a phosphorylation blocker and/or a 5′-stabilizedend cap.

A double-stranded short interfering nucleic acid (ds-siNA) moleculecomprises: (I) a sense strand comprising (A) a first nucleotide sequencethat is at least about 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, or 100%identical to an RNA corresponding to a target gene, wherein the firstnucleotide sequence: (i) is 15 to 30 nucleotides in length; and (ii)comprises 15 or more modified nucleotides independently selected from a2′-O-methyl nucleotide and a 2′-fluoro nucleotide, wherein at least onemodified nucleotide is a 2′-O-methyl nucleotide and at least onemodified nucleotide is a 2′-fluoro nucleotide; and (B) a phosphorylationblocker; and (II) an antisense strand comprising a second nucleotidesequence that is at least about 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%,or 100% complementary to the RNA corresponding to the target gene,wherein the second nucleotide sequence: (a) is 15 to 30 nucleotides inlength; and (b) comprises 15 or more modified nucleotides independentlyselected from a 2′-O-methyl nucleotide and a 2′-fluoro nucleotide,wherein at least one modified nucleotide is a 2′-O-methyl nucleotide andat least one modified nucleotide is a 2′-fluoro nucleotide.

A double-stranded short interfering nucleic acid (ds-siNA) molecule ofthe disclosure may comprise: (I) a sense strand comprising a firstnucleotide sequence that is at least about 60%, 65%, 70%, 75%, 80%, 85%,90%, 95%, or 100% identical to an RNA corresponding to a target gene,wherein the first nucleotide sequence: (a) is 15 to 30 nucleotides inlength; and (b) comprises 15 or more modified nucleotides independentlyselected from a 2′-O-methyl nucleotide and a 2′-fluoro nucleotide,wherein at least one modified nucleotide is a 2′-O-methyl nucleotide andat least one modified nucleotide is a 2′-fluoro nucleotide; and (II) anantisense strand comprising (A) a second nucleotide sequence that is atleast about 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, or 100%complementary to the RNA corresponding to the target gene, wherein thesecond nucleotide sequence: (i) is 15 to 30 nucleotides in length; and(ii) comprises 15 or more modified nucleotides independently selectedfrom a 2′-O-methyl nucleotide and a 2′-fluoro nucleotide, wherein atleast one modified nucleotide is a 2′-O-methyl nucleotide and at leastone modified nucleotide is a 2′-fluoro nucleotide; and (B) a5′-stabilized end cap.

A double-stranded short interfering nucleic acid (ds-siNA) molecule ofthe disclosure may comprise: (I) a sense strand comprising (A) a firstnucleotide sequence that is at least about 60%, 65%, 70%, 75%, 80%, 85%,90%, 95%, or 100% identical to an RNA corresponding to a target gene,wherein the first nucleotide sequence: (i) is 15 to 30 nucleotides inlength; and (ii) comprises 15 or more modified nucleotides independentlyselected from a 2′-O-methyl nucleotide and a 2′-fluoro nucleotide,wherein at least one modified nucleotide is a 2′-O-methyl nucleotide andat least one modified nucleotide is a 2′-fluoro nucleotide; and (B) aphosphorylation blocker; and (II) an antisense strand comprising (A) asecond nucleotide sequence that is at least about 60%, 65%, 70%, 75%,80%, 85%, 90%, 95%, or 100% complementary to the RNA corresponding tothe target gene, wherein the second nucleotide sequence: (i) is 15 to 30nucleotides in length; and (ii) comprises 15 or more modifiednucleotides independently selected from a 2′-O-methyl nucleotide and a2′-fluoro nucleotide, wherein at least one modified nucleotide is a2′-O-methyl nucleotide and at least one modified nucleotide is a2′-fluoro nucleotide; and (B) a 5′-stabilized end cap.

A double-stranded short interfering nucleic acid (ds-siNA) molecule ofthe disclosure may comprise: (a) a sense strand comprising a firstnucleotide sequence that is at least about 60%, 65%, 70%, 75%, 80%, 85%,90%, 95%, or 100% identical to an RNA corresponding to a target gene,wherein the first nucleotide sequence comprises a nucleotide sequence ofany one of the sequences disclosed in Table 1; and (b) an antisensestrand comprising a second nucleotide sequence that is at least about60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, or 100% complementary to the RNAcorresponding to the target gene, wherein the second nucleotide sequencecomprises a nucleotide sequence of any one of the sequences disclosed inTable 1.

A double-stranded short interfering nucleic acid (ds-siNA) moleculecomprises: (a) a sense strand comprising a first nucleotide sequencethat is at least about 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, or 100%identical to an RNA corresponding to a target gene, wherein the firstnucleotide sequence comprises a nucleotide sequence as shown in Table 2;and (b) an antisense strand comprising a second nucleotide sequence thatis at least about 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, or 100%complementary to the RNA corresponding to the target gene, wherein thesecond nucleotide sequence comprises a nucleotide sequence as shown inTable 2.

Further disclosed herein are compositions comprising two or more of thesiNA molecules described herein. Further disclosed herein arecompositions comprising any of the siNA molecule described and apharmaceutically acceptable carrier or diluent. Further disclosed hereinare compositions comprising two or more of the siNA molecules describedherein for use as a medicament. Further disclosed herein arecompositions comprising any of the siNA molecule described and apharmaceutically acceptable carrier or diluent for use as a medicament.

Further disclosed herein are methods of treating an infection (e.g.,COVID-19) in a subject in need thereof, the method comprisingadministering to the subject any of the siNA molecules described herein.Further disclosed herein are uses of any of the siNA molecules describedherein in the manufacture of a medicament for treating an infection(e.g., COVID-19).

A. siNA Sense Strand

Any of the siNA molecules or oligomers described herein may comprise asense strand. The sense strand may comprise a first nucleotide sequence.The first nucleotide sequence may be 15 to 30, 15 to 25, 15 to 23, 17 to23, 19 to 23, or 19 to 21 nucleotides in length. In some embodiments,the first nucleotide sequence is 15, 16, 17, 18, 19, 20, 21, 22, 23, 24,25, 26, 27, 28, 29, or 30 nucleotides in length. In some embodiments,the first nucleotide sequence is at least 19 nucleotides in length. Insome embodiments, the first nucleotide sequence is at least 21nucleotides in length.

In some embodiments, the sense strand is the same length as the firstnucleotide sequence. In some embodiments, the sense strand is longerthan the first nucleotide sequence. In some embodiments, the sensestrand may further comprise 1, 2, 3, 4, or 5 or more nucleotides thanthe first nucleotide sequence. In some embodiments, the sense strand mayfurther comprise a deoxyribonucleic acid (DNA). In some embodiments, theDNA is thymine (T). In some embodiments, the sense strand may furthercomprise a TT sequence. In some embodiments, the TT sequence is adjacentto the first nucleotide sequence. In some embodiments, the sense strandmay further comprise one or more modified nucleotides that are adjacentto the first nucleotide sequence. In some embodiments, the one or moremodified nucleotides are independently selected from any of the modifiednucleotides disclosed herein (e.g., 2′-fluoro nucleotide, 2′-O-methylnucleotide, 2′-fluoro nucleotide mimic, 2′-O-methyl nucleotide mimic, ora nucleotide comprising a modified nucleobase).

In some embodiments, at least one end of the ds-siNA may be a blunt end.In some embodiments, at least one end of the ds-siNA may comprise anoverhang, wherein the overhang comprises at least one nucleotide. Insome embodiments, both ends of the ds-siNA may comprise an overhang,wherein the overhang comprises at least one nucleotide.

In some embodiments, the first nucleotide sequence comprises 15, 16, 17,18, 19, 20, 21, 22, 23, or more modified nucleotides independentlyselected from a 2′-O-methyl nucleotide and a 2′-fluoro nucleotide. Insome embodiments, 70%, 75%, 80%, 85%, 90%, 95% or 100% of thenucleotides in the first nucleotide sequence are modified nucleotidesindependently selected from a 2′-O-methyl nucleotide and a 2′-fluoronucleotide. In some embodiments, 100% of the nucleotides in the firstnucleotide sequence are modified nucleotides independently selected froma 2′-O-methyl nucleotide and a 2′-fluoro nucleotide. In someembodiments, the 2′-O-methyl nucleotide is a 2′-O-methyl nucleotidemimic. In some embodiments, the 2′-fluoro nucleotide is a 2′-fluoronucleotide mimic.

In some embodiments, between about 15 to 30, 15 to 25, 15 to 24, 15 to23, 15 to 22, 15 to 21, 17 to 30, 17 to 25, 17 to 24, 17 to 23, 17 to22, 17 to 21, 18 to 30, 18 to 25, 18 to 24, 18 to 23, 18 to 22, 18 to21, 19 to 30, 19 to 25, 19 to 24, 19 to 23, 19 to 22, 19 to 21, 20 to25, 20 to 24, 20 to 23, 21 to 25, 21 to 24, or 21 to 23 modifiednucleotides of the first nucleotide sequence are 2′-O-methylnucleotides. In some embodiments, between about 2 to 20 modifiednucleotides of the first nucleotide sequence are 2′-O-methylnucleotides. In some embodiments, between about 5 to 25 modifiednucleotides of the first nucleotide sequence are 2′-O-methylnucleotides. In some embodiments, between about 10 to 25 modifiednucleotides of the first nucleotide sequence are 2′-O-methylnucleotides. In some embodiments, between about 12 to 25 modifiednucleotides of the first nucleotide sequence are 2′-O-methylnucleotides. In some embodiments, at least about 10, 11, 12, 13, 14, 15,16, 17, 18, 19, 20, 21, or 22 modified nucleotides of the firstnucleotide sequence are 2′-O-methyl nucleotides. In some embodiments, atleast about 12 modified nucleotides of the first nucleotide sequence are2′-O-methyl nucleotides. In some embodiments, at least about 13 modifiednucleotides of the first nucleotide sequence are 2′-O-methylnucleotides. In some embodiments, at least about 14 modified nucleotidesof the first nucleotide sequence are 2′-O-methyl nucleotides. In someembodiments, at least about 15 modified nucleotides of the firstnucleotide sequence are 2′-O-methyl nucleotides. In some embodiments, atleast about 16 modified nucleotides of the first nucleotide sequence are2′-O-methyl nucleotides. In some embodiments, at least about 17 modifiednucleotides of the first nucleotide sequence are 2′-O-methylnucleotides. In some embodiments, at least about 18 modified nucleotidesof the first nucleotide sequence are 2′-O-methyl nucleotides. In someembodiments, at least about 19 modified nucleotides of the firstnucleotide sequence are 2′-O-methyl nucleotides. In some embodiments,less than or equal to 25, 24, 23, 22, 21, 20, 19, 18, 17, 16, 15, 14,13, 12, 11, 10, 9, 8, 7, 6, 5, 4, 3, or 2 modified nucleotides of thefirst nucleotide sequence are 2′-O-methyl nucleotides. In someembodiments, less than or equal to 21 modified nucleotides of the firstnucleotide sequence are 2′-O-methyl nucleotides. In some embodiments,less than or equal to 20 modified nucleotides of the first nucleotidesequence are 2′-O-methyl nucleotides. In some embodiments, less than orequal to 19 modified nucleotides of the first nucleotide sequence are2′-O-methyl nucleotides. In some embodiments, less than or equal to 18modified nucleotides of the first nucleotide sequence are 2′-O-methylnucleotides. In some embodiments, less than or equal to 17 modifiednucleotides of the first nucleotide sequence are 2′-O-methylnucleotides. In some embodiments, less than or equal to 16 modifiednucleotides of the first nucleotide sequence are 2′-O-methylnucleotides. In some embodiments, less than or equal to 15 modifiednucleotides of the first nucleotide sequence are 2′-O-methylnucleotides. In some embodiments, less than or equal to 14 modifiednucleotides of the first nucleotide sequence are 2′-O-methylnucleotides. In some embodiments, less than or equal to 13 modifiednucleotides of the first nucleotide sequence are 2′-O-methylnucleotides. In some embodiments, at least one modified nucleotide ofthe first nucleotide sequence is a 2′-O-methyl pyrimidine. In someembodiments, at least 5, 6, 7, 8, 9, or 10 modified nucleotides of thefirst nucleotide sequence are 2′-O-methyl pyrimidines. In someembodiments, at least one modified nucleotide of the first nucleotidesequence is a 2′-O-methyl purine. In some embodiments, at least 5, 6, 7,8, 9, or 10 modified nucleotides of the first nucleotide sequence are2′-O-methyl purines. In some embodiments, the 2′-O-methyl nucleotide isa 2′-O-methyl nucleotide mimic.

In some embodiments, between 2 to 15 modified nucleotides of the firstnucleotide sequence are 2′-fluoro nucleotides. In some embodiments,between 2 to 10 modified nucleotides of the first nucleotide sequenceare 2′-fluoro nucleotides. In some embodiments, between 2 to 6 modifiednucleotides of the first nucleotide sequence are 2′-fluoro nucleotides.In some embodiments, 1 to 6, 1 to 5, 1 to 4, or 1 to 3 modifiednucleotides of the first nucleotide sequence are 2′-fluoro nucleotides.In some embodiments, at least 1, 2, 3, 4, 5, or 6 modified nucleotidesof the first nucleotide sequence are 2′-fluoro nucleotides. In someembodiments, at least 1 modified nucleotide of the first nucleotidesequence is a 2′-fluoro nucleotide. In some embodiments, at least 2modified nucleotides of the first nucleotide sequence are 2′-fluoronucleotides. In some embodiments, at least 3 modified nucleotides of thefirst nucleotide sequence are 2′-fluoro nucleotides. In someembodiments, at least 4 modified nucleotides of the first nucleotidesequence are 2′-fluoro nucleotides. In some embodiments, at least 5modified nucleotides of the first nucleotide sequence are 2′-fluoronucleotides. In some embodiments, at least 6 modified nucleotides of thefirst nucleotide sequence are 2′-fluoro nucleotides. In someembodiments, 10, 9, 8, 7, 6, 5, 4, 3 or fewer modified nucleotides ofthe first nucleotide sequence are 2′-fluoro nucleotides. In someembodiments, 10 or fewer modified nucleotides of the first nucleotidesequence are 2′-fluoro nucleotides. In some embodiments, 7 or fewermodified nucleotides of the first nucleotide sequence are 2′-fluoronucleotides. In some embodiments, 6 or fewer modified nucleotides of thefirst nucleotide sequence are 2′-fluoro nucleotides. In someembodiments, 5 or fewer modified nucleotides of the first nucleotidesequence are 2′-fluoro nucleotides. In some embodiments, 4 or fewermodified nucleotides of the first nucleotide sequence are 2′-fluoronucleotides. In some embodiments, 3 or fewer modified nucleotides of thefirst nucleotide sequence are 2′-fluoro nucleotides. In someembodiments, 2 or fewer modified nucleotides of the first nucleotidesequence are 2′-fluoro nucleotides. In some embodiments, at least onemodified nucleotide of the first nucleotide sequence is a 2′-fluoropyrimidine. In some embodiments, 1, 2, 3, 4, 5, or 6 modifiednucleotides of the first nucleotide sequence are 2′-fluoro pyrimidines.In some embodiments, at least one modified nucleotide of the firstnucleotide sequence is a 2′-fluoro purine. In some embodiments, 1, 2, 3,4, 5, or 6 modified nucleotides of the first nucleotide sequence are2′-fluoro purines. In some embodiments, the 2′-fluoro nucleotide is a2′-fluoro nucleotide mimic.

In some embodiments, the nucleotide at position 3, 5, 7, 8, 9, 10, 11,12, 14, 17, and/or 19 from the 5′ end of the first nucleotide sequenceis a 2′-fluoro nucleotide. In some embodiments, at least two nucleotidesat positions 3, 5, 7, 8, 9, 10, 11, 12, 14, 17, and/or 19 from the 5′end of the first nucleotide sequence are 2′-fluoro nucleotides. In someembodiments, at least three nucleotides at positions 3, 5, 7, 8, 9, 10,11, 12, 14, 17, and/or 19 from the 5′ end of the first nucleotidesequence are 2′-fluoro nucleotides. In some embodiments, at least fournucleotides at positions 3, 5, 7, 8, 9, 10, 11, 12, 14, 17, and/or 19from the 5′ end of the first nucleotide sequence are 2′-fluoronucleotides. In some embodiments, at least five nucleotides at positions3, 5, 7, 8, 9, 10, 11, 12, 14, 17, and/or 19 from the 5′ end of thefirst nucleotide sequence are 2′-fluoro nucleotides. In someembodiments, the nucleotides at positions 3, 5, 7, 8, 9, 10, 11, 12, 14,17, and/or 19 from the 5′ end of the first nucleotide sequence are2′-fluoro nucleotides. In some embodiments, the nucleotide at position 3from the 5′ end of the first nucleotide sequence is a 2′-fluoronucleotide. In some embodiments, the nucleotide at position 7 from the5′ end of the first nucleotide sequence is a 2′-fluoro nucleotide. Insome embodiments, the nucleotide at position 8 from the 5′ end of thefirst nucleotide sequence is a 2′-fluoro nucleotide. In someembodiments, the nucleotide at position 9 from the 5′ end of the firstnucleotide sequence is a 2′-fluoro nucleotide. In some embodiments, thenucleotide at position 12 from the 5′ end of the first nucleotidesequence is a 2′-fluoro nucleotide. In some embodiments, the nucleotideat position 17 from the 5′ end of the first nucleotide sequence is a2′-fluoro nucleotide. In some embodiments, the 2′-fluoro nucleotide is a2′-fluoro nucleotide mimic.

In some embodiments, at least 1, 2, 3, 4, 5, 6, or 7 nucleotides atposition 3, 5, 7, 8, 9, 10, 11, 12, 14, 17, and/or 19 from the 5′ end ofthe first nucleotide sequence is a 2′-fluoro nucleotide. In someembodiments, the nucleotide at positions 3, 5, 7, 8, 9, 10, 11, 12, 14,17, and/or 19 from the 5′ end of the first nucleotide sequence is a2′-fluoro nucleotide. In some embodiments, at least two nucleotides atpositions 3, 5, 7, 8, 9, 10, 11, 12, 14, 17, and/or 19 from the 5′ endof the first nucleotide sequence are 2′-fluoro nucleotides. In someembodiments, at least three nucleotides at positions 3, 5, 7, 8, 9, 10,11, 12, 14, 17, and/or 19 from the 5′ end of the first nucleotidesequence are 2′-fluoro nucleotides. In some embodiments, the nucleotidesat positions 3, 5, 7, 8, 9, 10, 11, 12, 14, 17, and/or 19 from the 5′end of the first nucleotide sequence are 2′-fluoro nucleotides. In someembodiments, the nucleotide at position 3 from the 5′ end of the firstnucleotide sequence is a 2′-fluoro nucleotide. In some embodiments, thenucleotide at position 5 from the 5′ end of the first nucleotidesequence is a 2′-fluoro nucleotide. In some embodiments, the nucleotideat position 7 from the 5′ end of the first nucleotide sequence is a2′-fluoro nucleotide. In some embodiments, the nucleotide at position 8from the 5′ end of the first nucleotide sequence is a 2′-fluoronucleotide. In some embodiments, the nucleotide at position 9 from the5′ end of the first nucleotide sequence is a 2′-fluoro nucleotide. Insome embodiments, the nucleotide at position 10 from the 5′ end of thefirst nucleotide sequence is a 2′-fluoro nucleotide. In someembodiments, the nucleotide at position 11 from the 5′ end of the firstnucleotide sequence is a 2′-fluoro nucleotide. In some embodiments, thenucleotide at position 12 from the 5′ end of the first nucleotidesequence is a 2′-fluoro nucleotide. In some embodiments, the nucleotideat position 14 from the 5′ end of the first nucleotide sequence is a2′-fluoro nucleotide. In some embodiments, the nucleotide at position 17from the 5′ end of the first nucleotide sequence is a 2′-fluoronucleotide. In some embodiments, the nucleotide at position 19 from the5′ end of the first nucleotide sequence is a 2′-fluoro nucleotide. Insome embodiments, the nucleotide at position 3, 7, 8, 9, 12, and/or 17from the 5′ end of the first nucleotide sequence is a 2′-fluoronucleotide. In some embodiments, the nucleotide at position 3, 7, 8,and/or 17 from the 5′ end of the first nucleotide sequence is a2′-fluoro nucleotide. In some embodiments, the nucleotide at position 3,7, 8, 9, 12, and/or 17 from the 5′ end of the first nucleotide sequenceis a 2′-fluoro nucleotide. In some embodiments, the nucleotide atposition 5, 7, 8, and/or 9 from the 5′ end of the first nucleotidesequence is a 2′-fluoro nucleotide. In some embodiments, the nucleotideat position 5, 9, 10, 11, 12, and/or 19 from the 5′ end of the firstnucleotide sequence is a 2′-fluoro nucleotide. In some embodiments, the2′-fluoro nucleotide is a 2′-fluoro nucleotide mimic. The 2′-fluoronucleotide mimic can be selected from

In some embodiments, the 2′-fluoro nucleotide or 2′-O-methyl nucleotideis a 2′-fluoro or 2′-O-methyl nucleotide mimic. In some embodiments, the2′-fluoro or 2′-O-methyl nucleotide mimic is a nucleotide mimic ofFormula (V):

wherein R¹ is a independently nucleobase, aryl, heteroaryl, or H, Q¹ andQ² are independently S or O, R⁵ is independently —OCD₃, —F, or —OCH₃,and R⁶ and R⁷ are independently H, D, or CD₃. In some embodiments, thenucleobase is selected from cytosine, guanine, adenine, uracil, aryl,heteroaryl, and an analogue or derivative thereof.

In some embodiments, the 2′-fluoro or 2′-O-methyl nucleotide mimic is anucleotide mimic of Formula (16)-Formula (20):

wherein R¹ is independently a nucleobase and R² is F or —OCH₃. In someembodiments, the nucleobase is selected from cytosine, guanine, adenine,uracil, aryl, heteroaryl, and an analogue or derivative thereof.

In some embodiments, the first nucleotide sequence comprises, consistsof, or consists essentially of ribonucleic acids (RNAs). In someembodiments, the first nucleotide sequence comprises, consists of, orconsists essentially of modified RNAs. In some embodiments, the modifiedRNAs are selected from a 2′-O-methyl RNA and 2′-fluoro RNA. In someembodiments, 15, 16, 17, 18, 19, 20, 21, 22, or 23 modified nucleotidesof the first nucleotide sequence are independently selected from2′-O-methyl RNA and 2′-fluoro RNA.

In some embodiments, the sense strand may further comprise one or moreinternucleoside linkages independently selected from a phosphodiester(PO) internucleoside linkage, phosphorothioate (PS) internucleosidelinkage, phosphorodithioate internucleoside linkage, and PS-mimicinternucleoside linkage. In some embodiments, the PS-mimicinternucleoside linkage is a sulfo internucleotide linkage.

In some embodiments, the sense strand may further comprise at least 1,2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, or 15 or morephosphorothioate internucleoside linkages. In some embodiments, thesense strand comprises 20, 19, 18, 17, 16, 15, 14, 13, 12, 11, 10, 9, 8,7, 6, 5, 4, or 3 or fewer phosphorothioate internucleoside linkages. Insome embodiments, the sense strand comprises 2 to 10, 2 to 8, 2 to 6, 1to 5, 1 to 4, 1 to 3, or 1 to 2 phosphorothioate internucleosidelinkages. In some embodiments, the sense strand comprises 1 to 2phosphorothioate internucleoside linkages. In some embodiments, thesense strand comprises 2 to 4 phosphorothioate internucleoside linkages.In some embodiments, at least one phosphorothioate internucleosidelinkage is between the nucleotides at positions 1 and 2 from the 5′ endof the first nucleotide sequence. In some embodiments, at least onephosphorothioate internucleoside linkage is between the nucleotides atpositions 2 and 3 from the 5′ end of the first nucleotide sequence. Insome embodiments, the sense strand comprises two phosphorothioateinternucleoside linkages between the nucleotides at positions 1 to 3from the 5′ end of the first nucleotide sequence.

In some embodiments, any of the sense strands disclosed herein maycomprise a 5′ end cap monomer. In some embodiments, any of the firstnucleotide sequences disclosed herein may comprise a 5′ end cap monomer.

B. siNA Antisense Strand

Any of the siNA molecules described herein may comprise an antisensestrand. The antisense strand may comprise a second nucleotide sequence.The second nucleotide sequence may be 15 to 30, 15 to 25, 15 to 23, 17to 23, 19 to 23, or 19 to 21 nucleotides in length. In some embodiments,the second nucleotide sequence is 15, 16, 17, 18, 19, 20, 21, 22, 23,24, 25, 26, 27, 28, 29, or 30 nucleotides in length. In someembodiments, the second nucleotide sequence is at least 19 nucleotidesin length. In some embodiments, the second nucleotide sequence is atleast 21 nucleotides in length.

In some embodiments, the antisense strand is the same length as thesecond nucleotide sequence. In some embodiments, the antisense strand islonger than the second nucleotide sequence. In some embodiments, theantisense strand may further comprise 1, 2, 3, 4, or 5 or morenucleotides than the second nucleotide sequence. In some embodiments,the antisense strand is the same length as the sense strand. In someembodiments, the antisense strand is longer than the sense strand. Insome embodiments, the antisense strand may further comprise 1, 2, 3, 4,or 5 or more nucleotides than the sense strand. In some embodiments, theantisense strand may further comprise a deoxyribonucleic acid (DNA). Insome embodiments, the DNA is thymine (T). In some embodiments, theantisense strand may further comprise a TT sequence. In someembodiments, the antisense strand may further comprise one or moremodified nucleotides that are adjacent to the second nucleotidesequence. In some embodiments, the one or more modified nucleotides areindependently selected from any of the modified nucleotides disclosedherein (e.g., 2′-fluoro nucleotide, 2′-O-methyl nucleotide, 2′-fluoronucleotide mimic, 2′-O-methyl nucleotide mimic, or a nucleotidecomprising a modified nucleobase).

In some embodiments, the second nucleotide sequence comprises 15, 16,17, 18, 19, 20, 21, 22, 23, or more modified nucleotides independentlyselected from a 2′-O-methyl nucleotide and a 2′-fluoro nucleotide. Insome embodiments, 70%, 75%, 80%, 85%, 90%, 95% or 100% of thenucleotides in the second nucleotide sequence are modified nucleotidesindependently selected from a 2′-O-methyl nucleotide and a 2′-fluoronucleotide. In some embodiments, 100% of the nucleotides in the secondnucleotide sequence are modified nucleotides independently selected froma 2′-O-methyl nucleotide and a 2′-fluoro nucleotide.

In some embodiments, between about 15 to 30, 15 to 25, 15 to 24, 15 to23, 15 to 22, 15 to 21, 17 to 30, 17 to 25, 17 to 24, 17 to 23, 17 to22, 17 to 21, 18 to 30, 18 to 25, 18 to 24, 18 to 23, 18 to 22, 18 to21, 19 to 30, 19 to 25, 19 to 24, 19 to 23, 19 to 22, 19 to 21, 20 to25, 20 to 24, 20 to 23, 21 to 25, 21 to 24, or 21 to 23 modifiednucleotides of the second nucleotide sequence are 2′-O-methylnucleotides. In some embodiments, between about 2 to 20 modifiednucleotides of the second nucleotide sequence are 2′-O-methylnucleotides. In some embodiments, between about 5 to 25 modifiednucleotides of the second nucleotide sequence are 2′-O-methylnucleotides. In some embodiments, between about 10 to 25 modifiednucleotides of the second nucleotide sequence are 2′-O-methylnucleotides. In some embodiments, between about 12 to 25 modifiednucleotides of the second nucleotide sequence are 2′-O-methylnucleotides. In some embodiments, at least 10, 11, 12, 13, 14, 15, 16,17, 18, 19, 20, 21, or 22 modified nucleotides of the second nucleotidesequence are 2′-O-methyl nucleotides. In some embodiments, at leastabout 12 modified nucleotides of the second nucleotide sequence are2′-O-methyl nucleotides. In some embodiments, at least about 13 modifiednucleotides of the second nucleotide sequence are 2′-O-methylnucleotides. In some embodiments, at least about 14 modified nucleotidesof the second nucleotide sequence are 2′-O-methyl nucleotides. In someembodiments, at least about 15 modified nucleotides of the secondnucleotide sequence are 2′-O-methyl nucleotides. In some embodiments, atleast about 16 modified nucleotides of the second nucleotide sequenceare 2′-O-methyl nucleotides. In some embodiments, at least about 17modified nucleotides of the second nucleotide sequence are 2′-O-methylnucleotides. In some embodiments, at least about 18 modified nucleotidesof the second nucleotide sequence are 2′-O-methyl nucleotides. In someembodiments, at least about 19 modified nucleotides of the secondnucleotide sequence are 2′-O-methyl nucleotides. In some embodiments,less than or equal to 25, 24, 23, 22, 21, 20, 19, 18, 17, 16, 15, 14,13, 12, 11, 10, 9, 8, 7, 6, 5, 4, 3, or 2 modified nucleotides of thesecond nucleotide sequence are 2′-O-methyl nucleotides. In someembodiments, less than or equal to 21 modified nucleotides of the secondnucleotide sequence are 2′-O-methyl nucleotides. In some embodiments,less than or equal to 20 modified nucleotides of the second nucleotidesequence are 2′-O-methyl nucleotides. In some embodiments, less than orequal to 19 modified nucleotides of the second nucleotide sequence are2′-O-methyl nucleotides. In some embodiments, less than or equal to 18modified nucleotides of the second nucleotide sequence are 2′-O-methylnucleotides. In some embodiments, less than or equal to 17 modifiednucleotides of the second nucleotide sequence are 2′-O-methylnucleotides. In some embodiments, less than or equal to 16 modifiednucleotides of the second nucleotide sequence are 2′-O-methylnucleotides. In some embodiments, less than or equal to 15 modifiednucleotides of the second nucleotide sequence are 2′-O-methylnucleotides. In some embodiments, less than or equal to 14 modifiednucleotides of the second nucleotide sequence are 2′-O-methylnucleotides. In some embodiments, less than or equal to 13 modifiednucleotides of the second nucleotide sequence are 2′-O-methylnucleotides. In some embodiments, at least one modified nucleotide ofthe second nucleotide sequence is a 2′-O-methyl pyrimidine. In someembodiments, at least 5, 6, 7, 8, 9, or 10 modified nucleotides of thesecond nucleotide sequence are 2′-O-methyl pyrimidines. In someembodiments, at least one modified nucleotide of the second nucleotidesequence is a 2′-O-methyl purine. In some embodiments, at least 5, 6, 7,8, 9, or 10 modified nucleotides of the second nucleotide sequence are2′-O-methyl purines. In some embodiments, the 2′-O-methyl nucleotide isa 2′-O-methyl nucleotide mimic.

In some embodiments, between 2 to 15 modified nucleotides of the secondnucleotide sequence are 2′-fluoro nucleotides. In some embodiments,between 2 to 10 modified nucleotides of the second nucleotide sequenceare 2′-fluoro nucleotides. In some embodiments, between 2 to 6 modifiednucleotides of the second nucleotide sequence are 2′-fluoro nucleotides.In some embodiments, 1 to 6, 1 to 5, 1 to 4, or 1 to 3 modifiednucleotides of the second nucleotide sequence are 2′-fluoro nucleotides.In some embodiments, at least 1, 2, 3, 4, 5, or 6 modified nucleotidesof the second nucleotide sequence are 2′-fluoro nucleotides. In someembodiments, at least 1 modified nucleotide of the second nucleotidesequence is a 2′-fluoro nucleotide. In some embodiments, at least 2modified nucleotides of the second nucleotide sequence are 2′-fluoronucleotides. In some embodiments, at least 3 modified nucleotides of thesecond nucleotide sequence are 2′-fluoro nucleotides. In someembodiments, at least 4 modified nucleotides of the second nucleotidesequence are 2′-fluoro nucleotides. In some embodiments, at least 5modified nucleotides of the second nucleotide sequence are 2′-fluoronucleotides. In some embodiments, 10, 9, 8, 7, 6, 5, 4, 3 or fewermodified nucleotides of the second nucleotide sequence are 2′-fluoronucleotides. In some embodiments, 10 or fewer modified nucleotides ofthe second nucleotide sequence are 2′-fluoro nucleotides. In someembodiments, 7 or fewer modified nucleotides of the second nucleotidesequence are 2′-fluoro nucleotides. In some embodiments, 6 or fewermodified nucleotides of the second nucleotide sequence are 2′-fluoronucleotides. In some embodiments, 5 or fewer modified nucleotides of thesecond nucleotide sequence are 2′-fluoro nucleotides. In someembodiments, 4 or fewer modified nucleotides of the second nucleotidesequence are 2′-fluoro nucleotides. In some embodiments, 3 or fewermodified nucleotides of the second nucleotide sequence are 2′-fluoronucleotides. In some embodiments, 2 or fewer modified nucleotides of thesecond nucleotide sequence are 2′-fluoro nucleotides. In someembodiments, at least one modified nucleotide of the second nucleotidesequence is a 2′-fluoro pyrimidine. In some embodiments, 1, 2, 3, 4, 5,or 6 modified nucleotides of the second nucleotide sequence are2′-fluoro pyrimidines. In some embodiments, at least one modifiednucleotide of the second nucleotide sequence is a 2′-fluoro purine. Insome embodiments, 1, 2, 3, 4, 5, or 6 modified nucleotides of the secondnucleotide sequence are 2′-fluoro purines. In some embodiments, the2′-fluoro nucleotide is a 2′-fluoro nucleotide mimic. The 2′-fluoronucleotide mimic can be selected from

In some embodiments, the 2′-fluoro nucleotide or 2′-O-methyl nucleotideis a 2′-fluoro or 2′-O-methyl nucleotide mimic. In some embodiments, the2′-fluoro or 2′-O-methyl nucleotide mimic is a nucleotide mimic ofFormula (V):

wherein R¹ is independently a nucleobase, aryl, heteroaryl, or H, Q¹ andQ² are independently S or O, R⁵ is independently —OCD₃, —F, or —OCH₃,and R⁶ and R⁷ are independently H, D, or CD₃. In some embodiments, thenucleobase is selected from cytosine, guanine, adenine, uracil, aryl,heteroaryl, and an analogue or derivative thereof.

In some embodiments, the 2′-fluoro or 2′-O-methyl nucleotide mimic is anucleotide mimic of Formula (16)-Formula (20):

wherein R¹ is a nucleobase and R² is independently F or —OCH₃. In someembodiments, the nucleobase is selected from cytosine, guanine, adenine,uracil, aryl, heteroaryl, and an analogue or derivative thereof.

In some embodiments, at least 1, 2, 3, 4, 5, 6, 7, 8, or 9 nucleotidesat position 2, 5, 6, 8, 10, 14, 16, 17, and/or 18 from the 5′ end of thesecond nucleotide sequence is a 2′-fluoro nucleotide. In someembodiments, the nucleotide at position 2, 5, 6, 8, 10, 14, 16, 17,and/or 18 from the 5′ end of the second nucleotide sequence is a2′-fluoro nucleotide. In some embodiments, at least two nucleotides atpositions 2, 5, 6, 8, 10, 14, 16, 17, and/or 18 from the 5′ end of thesecond nucleotide sequence are 2′-fluoro nucleotides. In someembodiments, at least three nucleotides at positions 2, 5, 6, 8, 10, 14,16, 17, and/or 18 from the 5′ end of the second nucleotide sequence are2′-fluoro nucleotides. In some embodiments, at least four nucleotides atpositions 2, 5, 6, 8, 10, 14, 16, 17, and/or 18 from the 5′ end of thesecond nucleotide sequence are 2′-fluoro nucleotides. In someembodiments, at least five nucleotides at positions 2, 5, 6, 8, 10, 14,16, 17, and/or 18 from the 5′ end of the second nucleotide sequence are2′-fluoro nucleotides. In some embodiments, the nucleotides at positions2 and/or 14 from the 5′ end of the second nucleotide sequence are2′-fluoro nucleotides. In some embodiments, the nucleotides at positions2, 6, and/or 16 from the 5′ end of the second nucleotide sequence are2′-fluoro nucleotides. In some embodiments, the nucleotides at positions2, 6, 14, and/or 16 from the 5′ end of the second nucleotide sequenceare 2′-fluoro nucleotides. In some embodiments, the nucleotides atpositions 2, 6, 10, 14, and/or 18 from the 5′ end of the secondnucleotide sequence are 2′-fluoro nucleotides. In some embodiments, thenucleotides at positions 2, 5, 8, 14, and/or 17 from the 5′ end of thesecond nucleotide sequence are 2′-fluoro nucleotides. In someembodiments, the nucleotide at position 2 from the 5′ end of the secondnucleotide sequence is a 2′-fluoro nucleotide. In some embodiments, thenucleotide at position 5 from the 5′ end of the second nucleotidesequence is a 2′-fluoro nucleotide. In some embodiments, the nucleotideat position 6 from the 5′ end of the second nucleotide sequence is a2′-fluoro nucleotide. In some embodiments, the nucleotide at position 8from the 5′ end of the second nucleotide sequence is a 2′-fluoronucleotide. In some embodiments, the nucleotide at position 10 from the5′ end of the second nucleotide sequence is a 2′-fluoro nucleotide. Insome embodiments, the nucleotide at position 14 from the 5′ end of thesecond nucleotide sequence is a 2′-fluoro nucleotide. In someembodiments, the nucleotide at position 16 from the 5′ end of the secondnucleotide sequence is a 2′-fluoro nucleotide. In some embodiments, thenucleotide at position 17 from the 5′ end of the second nucleotidesequence is a 2′-fluoro nucleotide. In some embodiments, the nucleotideat position 18 from the 5′ end of the second nucleotide sequence is a2′-fluoro nucleotide. In some embodiments, the 2′-fluoro nucleotide is a2′-fluoro nucleotide mimic. The 2′-fluoro nucleotide mimic can beselected from

In some embodiments, the nucleotides in the second nucleotide sequenceare arranged in an alternating 1:3 modification pattern, wherein 1nucleotide is a 2′-fluoro nucleotide and 3 nucleotides are 2′-O-methylnucleotides, and wherein the alternating 1:3 modification pattern occursat least 2 times. In some embodiments, the alternating 1:3 modificationpattern occurs 2-5 times. In some embodiments, at least two of thealternating 1:3 modification pattern occur consecutively. In someembodiments, at least two of the alternating 1:3 modification patternoccurs nonconsecutively. In some embodiments, at least 1, 2, 3, 4, or 5alternating 1:3 modification pattern begins at nucleotide position 2, 6,10, 14, and/or 18 from the 5′ end of the antisense strand. In someembodiments, at least one alternating 1:3 modification pattern begins atnucleotide position 2 from the 5′ end of the antisense strand. In someembodiments, wherein at least one alternating 1:3 modification patternbegins at nucleotide position 6 from the 5′ end of the antisense strand.In some embodiments, at least one alternating 1:3 modification patternbegins at nucleotide position 10 from the 5′ end of the antisensestrand. In some embodiments, at least one alternating 1:3 modificationpattern begins at nucleotide position 14 from the 5′ end of theantisense strand. In some embodiments, at least one alternating 1:3modification pattern begins at nucleotide position 18 from the 5′ end ofthe antisense strand. In some embodiments, the 2′-fluoro nucleotide is a2′-fluoro nucleotide mimic. The 2′-fluoro nucleotide mimic can beselected from

In some embodiments, the nucleotides in the second nucleotide sequenceare arranged in an alternating 1:2 modification pattern, wherein 1nucleotide is a 2′-fluoro nucleotide and 2 nucleotides are 2′-O-methylnucleotides, and wherein the alternating 1:2 modification pattern occursat least 2 times. In some embodiments, the alternating 1:2 modificationpattern occurs 2-5 times. In some embodiments, at least two of thealternating 1:2 modification pattern occurs consecutively. In someembodiments, at least two of the alternating 1:2 modification patternoccurs nonconsecutively. In some embodiments, at least 1, 2, 3, 4, or 5alternating 1:2 modification pattern begins at nucleotide position 2, 5,8, 14, and/or 17 from the 5′ end of the antisense strand. In someembodiments, at least one alternating 1:2 modification pattern begins atnucleotide position 2 from the 5′ end of the antisense strand. In someembodiments, at least one alternating 1:2 modification pattern begins atnucleotide position 5 from the 5′ end of the antisense strand. In someembodiments, at least one alternating 1:2 modification pattern begins atnucleotide position 8 from the 5′ end of the antisense strand. In someembodiments, at least one alternating 1:2 modification pattern begins atnucleotide position 14 from the 5′ end of the antisense strand. In someembodiments, at least one alternating 1:2 modification pattern begins atnucleotide position 17 from the 5′ end of the antisense strand. In someembodiments, the 2′-fluoro nucleotide is a 2′-fluoro nucleotide mimic.The 2′-fluoro nucleotide mimic can be selected from

In some embodiments, the second nucleotide sequence comprises, consistsof, or consists essentially of ribonucleic acids (RNAs). In someembodiments, the second nucleotide sequence comprises, consists of, orconsists essentially of modified RNAs. In some embodiments, the modifiedRNAs are selected from a 2′-O-methyl RNA and 2′-fluoro RNA. In someembodiments, 15, 16, 17, 18, 19, 20, 21, 22, or 23 modified nucleotidesof the second nucleotide sequence are independently selected from2′-O-methyl RNA and 2′-fluoro RNA. In some embodiments, the 2′-fluoronucleotide is a 2′-fluoro nucleotide mimic. The 2′-fluoro nucleotidemimic can be selected from

In some embodiments, the sense strand may further comprise one or moreinternucleotide linkages independently selected from a phosphodiester(PO) internucleoside linkage, phosphorothioate (PS) internucleosidelinkage, phosphorodithioate internucleoside linkage, and PS-mimicinternucleoside linkage. In some embodiments, the PS-mimicinternucleoside linkage is a sulfo internucleotide linkage.

In some embodiments, the antisense strand may further comprise at least1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, or 15 or morephosphorothioate internucleoside linkages. In some embodiments, theantisense strand comprises 20, 19, 18, 17, 16, 15, 14, 13, 12, 11, 10,9, 8, 7, 6, 5, 4, or 3 or fewer phosphorothioate internucleosidelinkages. In some embodiments, the antisense strand comprises 2 to 10, 2to 8, 2 to 6, 1 to 5, 1 to 4, 1 to 3, or 1 to 2 phosphorothioateinternucleoside linkages. In some embodiments, the antisense strandcomprises 2 to 10, 2 to 8, 2 to 6, 1 to 5, 1 to 4, 1 to 3, or 1 to 2phosphorothioate internucleoside linkages. In some embodiments, theantisense strand comprises 2 to 8 phosphorothioate internucleosidelinkages. In some embodiments, the antisense strand comprises 3 to 8phosphorothioate internucleoside linkages. In some embodiments, theantisense strand comprises 4 to 8 phosphorothioate internucleosidelinkages. In some embodiments, at least one phosphorothioateinternucleoside linkage is between the nucleotides at positions 1 and 2from the 5′ end of the second nucleotide sequence. In some embodiments,at least one phosphorothioate internucleoside linkage is between thenucleotides at positions 2 and 3 from the 5′ end of the secondnucleotide sequence.

In some embodiments, at least one phosphorothioate internucleosidelinkage is between the nucleotides at positions 1 and 2 from the 3′ endof the second nucleotide sequence. In some embodiments, at least onephosphorothioate internucleoside linkage is between the nucleotides atpositions 2 and 3 from the 3′ end of the second nucleotide sequence. Insome embodiments, the antisense strand comprises two phosphorothioateinternucleoside linkages between the nucleotides at positions 1 to 3from the 5′ end of the first nucleotide sequence. In some embodiments,the antisense strand comprises two phosphorothioate internucleosidelinkages between the nucleotides at positions 1 to 3 from the 3′ end ofthe first nucleotide sequence. In some embodiments, the antisense strandcomprises (a) two phosphorothioate internucleoside linkages between thenucleotides at positions 1 to 3 from the 5′ end of the first nucleotidesequence; and (b) two phosphorothioate internucleoside linkages betweenthe nucleotides at positions 1 to 3 from the 3′ end of the firstnucleotide sequence.

In some embodiments, at least one end of the ds-siNA is a blunt end. Insome embodiments, at least one end of the ds-siNA comprises an overhang,wherein the overhang comprises at least one nucleotide. In someembodiments, both ends of the ds-siNA comprise an overhang, wherein theoverhang comprises at least one nucleotide. In some embodiments, theoverhang comprises 1 to 5 nucleotides, 1 to 4 nucleotides, 1 to 3nucleotides, or 1 to 2 nucleotides. In some embodiments, the overhangconsists of 1 to 2 nucleotides.

In some embodiments, any of the antisense strands disclosed herein maycomprise a 5′ end cap monomer. In some embodiments, any of the secondnucleotide sequences disclosed herein may comprise a 5′ end cap monomer.

Modified Nucleotides

Further disclosed herein are siNA molecules comprising one or moremodified nucleotides. In some embodiments, any of the siNAs disclosedherein comprise one or more modified nucleotides. In some embodiments,any of the sense strands disclosed herein comprise one or more modifiednucleotides. In some embodiments, any of the first nucleotide sequencesdisclosed herein comprise one or more modified nucleotides. In someembodiments, any of the antisense strands disclosed herein comprise oneor more modified nucleotides. In some embodiments, any of the secondnucleotide sequences disclosed herein comprise one or more modifiednucleotides. In some embodiments, the one or more modified nucleotidesis adjacent to the first nucleotide sequence. In some embodiments, atleast one modified nucleotide is adjacent to the 5′ end of the firstnucleotide sequence. In some embodiments, at least one modifiednucleotide is adjacent to the 3′ end of the first nucleotide sequence.In some embodiments, at least one modified nucleotide is adjacent to the5′ end of the first nucleotide sequence and at least one modifiednucleotide is adjacent to the 3′ end of the first nucleotide sequence.In some embodiments, the one or more modified nucleotides is adjacent tothe second nucleotide sequence. In some embodiments, at least onemodified nucleotide is adjacent to the 5′ end of the second nucleotidesequence. In some embodiments, at least one modified nucleotide isadjacent to the 3′ end of the second nucleotide sequence. In someembodiments, at least one modified nucleotide is adjacent to the 5′ endof the second nucleotide sequence and at least one modified nucleotideis adjacent to the 3′ end of the second nucleotide sequence. In someembodiments, a 2′-O-methyl nucleotide in any of sense strands or firstnucleotide sequences disclosed herein is replaced with a modifiednucleotide. In some embodiments, a 2′-O-methyl nucleotide in any ofantisense strands or second nucleotide sequences disclosed herein isreplaced with a modified nucleotide.

In some embodiments, any of the siNA molecules, siNAs, sense strands,first nucleotide sequences, antisense strands, and second nucleotidesequences disclosed herein comprise 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11,12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29,or 30 or more modified nucleotides. In some embodiments, 1%, 2%, 3%, 4%,5%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 70%, 75%,80%, 85%, 86%, 87%, 88%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%,99% or 100% of the nucleotides in the siNA molecule, siNA, sense strand,first nucleotide sequence, antisense strand, or second nucleotidesequence are modified nucleotides.

In some embodiments, a modified nucleotide is selected from the groupconsisting of 2′-fluoro nucleotide, 2′-O-methyl nucleotide, 2′-fluoronucleotide mimic, 2′-O-methyl nucleotide mimic, a locked nucleic acid,and a nucleotide comprising a modified nucleobase.

In some embodiments, any of the siRNAs disclosed herein comprise atleast 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 or more 2′-fluoro or 2′-O-methylnucleotide mimics. In some embodiments, any of the sense strandsdisclosed herein comprise at least 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 ormore 2′-fluoro or 2′-O-methyl nucleotide mimics. In some embodiments,any of the first nucleotide sequences disclosed herein comprise at least1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 or more 2′-fluoro or 2′-O-methylnucleotide mimics. In some embodiments, any of the antisense stranddisclosed herein comprise at least 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 ormore 2′-fluoro or 2′-O-methyl nucleotide mimics. In some embodiments,any of the second nucleotide sequences disclosed herein comprise atleast 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 or more 2′-fluoro or 2′-O-methylnucleotide mimics. In some embodiments, the 2′-fluoro or 2′-O-methylnucleotide mimic is a nucleotide mimic of Formula (16)-Formula (20):

wherein R¹ is a nucleobase and R¹ is independently F or —OCH₃. In someembodiments, the nucleobase is selected from cytosine, guanine, adenine,uracil, aryl, heteroaryl, and an analogue or derivative thereof.

In some embodiments, the siNA molecules disclosed herein comprise atleast one 2′-fluoro nucleotide, at least one 2′-O-methyl nucleotide, andat least one 2′-fluoro or 2′-O-methyl nucleotide mimic. In someembodiments, the at least one 2′-fluoro or 2′-O-methyl nucleotide mimicis adjacent to the first nucleotide sequence. In some embodiments, theat least one 2′-fluoro or 2′-O-methyl nucleotide mimic is adjacent tothe 5′ end of first nucleotide sequence. In some embodiments, the atleast one 2′-fluoro or 2′-O-methyl nucleotide mimic is adjacent to the3′ end of first nucleotide sequence. In some embodiments, the at leastone 2′-fluoro or 2′-O-methyl nucleotide mimic is adjacent to the secondnucleotide sequence. In some embodiments, the at least one 2′-fluoro or2′-O-methyl nucleotide mimic is adjacent to the 5′ end of secondnucleotide sequence. In some embodiments, the at least one 2′-fluoro or2′-O-methyl nucleotide mimic is adjacent to the 3′ end of secondnucleotide sequence. In some embodiments, the first nucleotide sequencedoes not comprise a 2′-fluoro nucleotide mimic. In some embodiments, thefirst nucleotide sequence does not comprise a 2′-O-methyl nucleotidemimic. In some embodiments, the second nucleotide sequence does notcomprise a 2′-fluoro nucleotide mimic. In some embodiments, the secondnucleotide sequence does not comprise a 2′-O-methyl nucleotide mimic.

In some embodiments, any of the siRNAs disclosed herein comprise atleast 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 or more locked nucleic acids. Insome embodiments, any of the sense strands disclosed herein comprise atleast 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 or more locked nucleic acids. Insome embodiments, any of the first nucleotide sequences disclosed hereincomprise at least 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 or more lockednucleic acids. In some embodiments, any of the antisense stranddisclosed herein comprise at least 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 ormore locked nucleic acids. In some embodiments, any of the secondnucleotide sequences disclosed herein comprise at least 1, 2, 3, 4, 5,6, 7, 8, 9, or 10 or more locked nucleic acids. In some embodiments, thelocked nucleic acid is selected from

where R is H or alkyl (or AmNA(N-Me)) when R is alkyl);

wherein B is a nucleobase. In some embodiments, any of the siRNAs, sensestrands, first nucleotide sequences, antisense strands, or secondnucleotide sequences disclosed herein comprise at least modifiednucleotide that is

In some embodiments, any of the siRNAs, sense strands, first nucleotidesequences, antisense strands, or second nucleotide sequences disclosedherein comprise at least modified nucleotide that is

In some embodiments, any of the siRNAs, sense strands, first nucleotidesequences, antisense strands, or second nucleotide sequences disclosedherein comprise at least modified nucleotide that is

where R is H or alkyl (or AmNA(N-Me)) when R is alkyl). In someembodiments, any of the siRNAs, sense strands, first nucleotidesequences, antisense strands, or second nucleotide sequences disclosedherein comprise at least modified nucleotide that is

In some embodiments, any of the siRNAs, sense strands, first nucleotidesequences, antisense strands, or second nucleotide sequences disclosedherein comprise at least modified nucleotide that is

wherein B is a nucleobase.

Phosphorylation Blocker

Further disclosed herein are siNA molecules comprising a phosphorylationblocker. In some embodiments, a 2′-O-methyl nucleotide in any of sensestrands or first nucleotide sequences disclosed herein is replaced witha nucleotide containing a phosphorylation blocker. In some embodiments,a 2′-O-methyl nucleotide in any of antisense strands or secondnucleotide sequences disclosed herein is replaced with a nucleotidecontaining a phosphorylation blocker. In some embodiments, a 2′-O-methylnucleotide in any of sense strands or first nucleotide sequencesdisclosed herein is further modified to contain a phosphorylationblocker. In some embodiments, a 2′-O-methyl nucleotide in any ofantisense strands or second nucleotide sequences disclosed herein isfurther modified to contain a phosphorylation blocker.

In some embodiments, any of the siNA molecules disclosed herein comprisea phosphorylation blocker of Formula (IV):

wherein R¹ is a nucleobase, R⁴ is —O—R³⁰ or —NR³¹R³², R³⁰ is C₁-C₈substituted or unsubstituted alkyl; and R³¹ and R³² together with thenitrogen to which they are attached form a substituted or unsubstitutedheterocyclic ring.

In some embodiments, any of the siNA molecules disclosed herein comprisea phosphorylation blocker of Formula (IV):

wherein R¹ is a nucleobase, and R⁴ is —OCH₃ or —N(CH₂CH₂)₂O.

In some embodiments, a siNA molecule comprises (a) a phosphorylationblocker of Formula (IV):

wherein R¹ is a nucleobase, R⁴ is —O—R³⁰ or —NR³¹R³², R³⁰ is C₁-C₈substituted or unsubstituted alkyl; and R³¹ and R³² together with thenitrogen to which they are attached form a substituted or unsubstitutedheterocyclic ring; and (b) a siNA, wherein the phosphorylation blockeris conjugated to the siNA.

In some embodiments, a siNA molecule comprises (a) a phosphorylationblocker of Formula (IV):

wherein R¹ is a nucleobase, and R⁴ is —OCH₃ or —N(CH₂CH₂)₂O; and (b)siNA, wherein the phosphorylation blocker is conjugated to the siNA.

In some embodiments, the phosphorylation blocker is attached to the 3′end of the sense strand or first nucleotide sequence. In someembodiments, the phosphorylation blocker is attached to the 3′ end ofthe sense strand or first nucleotide sequence via 1, 2, 3, 4, or 5 ormore linkers. In some embodiments, the phosphorylation blocker isattached to the 5′ end of the sense strand or first nucleotide sequence.In some embodiments, the phosphorylation blocker is attached to the 5′end of the sense strand or first nucleotide sequence via 1, 2, 3, 4, or5 or more linkers. In some embodiments, the phosphorylation blocker isattached to the 3′ end of the antisense strand or second nucleotidesequence. In some embodiments, the phosphorylation blocker is attachedto the 3′ end of the antisense strand or second nucleotide sequence via1, 2, 3, 4, or 5 or more linkers. In some embodiments, thephosphorylation blocker is attached to the 5′ end of the antisensestrand or second nucleotide sequence. In some embodiments, thephosphorylation blocker is attached to the 5′ end of the antisensestrand or second nucleotide sequence via 1, 2, 3, 4, or 5 or morelinkers. In some embodiments, the one or more linkers are independentlyselected from the group consisting of a phosphodiester linker,phosphorothioate linker, and phosphorodithioate linker.

5′-Stabilized End Cap

Further disclosed herein are siNA molecules comprising a 5′-stabilizedend cap. As used herein the terms “5′-stabilized end cap” and “5′ endcap” are used interchangeably. In some embodiments, a 2′-O-methylnucleotide in any of sense strands or first nucleotide sequencesdisclosed herein is replaced with a nucleotide containing a5′-stabilized end cap. In some embodiments, a 2′-O-methyl nucleotide inany of antisense strands or second nucleotide sequences disclosed hereinis replaced with a nucleotide containing a 5′-stabilized end cap. Insome embodiments, a 2′-O-methyl nucleotide in any of sense strands orfirst nucleotide sequences disclosed herein is further modified tocontain a 5′-stabilized end cap. In some embodiments, a 2′-O-methylnucleotide in any of antisense strands or second nucleotide sequencesdisclosed herein is further modified to contain a 5′-stabilized end cap.

In some embodiments, the 5′-stabilized end cap is a 5′ phosphate mimic.In some embodiments, the 5′-stabilized end cap is a modified 5′phosphate mimic. In some embodiments, the modified 5′ phosphate is achemically modified 5′ phosphate. In some embodiments, the 5′-stabilizedend cap is a 5′-vinyl phosphonate. In some embodiments, the 5′-vinylphosphonate is a 5′-(E)-vinyl phosphonate or 5′-(Z)-vinyl phosphonate.In some embodiments, the 5′-vinylphosphonate is a deuterated vinylphosphonate. In some embodiments, the deuterated vinyl phosphonate is amono-deuterated vinyl phosphonate. In some embodiments, the deuteratedvinyl phosphonate is a di-deuterated vinyl phosphonate. In someembodiments, the 5′-stabilized end cap is a phosphate mimic. Examples ofphosphate mimics are disclosed in Parmar et al., 2018, J Med Chem,61(3):734-744, International Publication Nos. WO2018/045317 andWO2018/044350, and U.S. Pat. No. 10,087,210, each of which isincorporated by reference in its entirety.

In some embodiments, any of the siNA molecules, sense strands, firstnucleotide sequences, antisense strands, or second nucleotide sequencesdisclosed herein comprise a 5′-stabilized end cap of Formula (Ia):

wherein R¹ is H, a nucleobase, aryl, or heteroaryl; R² is

—CH═CD-Z, —CD=CH—Z, —CD=CD-Z, —(CR²¹R²²)_(n)—Z, or —(C₂-C₆ alkenylene)-Zand R²⁰ is H; or R² and R²⁰ together form a 3- to 7-membered carbocyclicring substituted with —(CR²¹R²²)_(n)—Z or —(C₂-C₆ alkenylene)-Z; n is 1,2, 3, or 4; Z is —ONR²³R²⁴, —OP(O)OH(CH₂)_(m)CO₂R²³,—OP(S)OH(CH₂)_(m)CO₂R²³, —P(O)(OH)₂, —P(O)(OH)(OCH₃), —P(O)(OH)(OCD₃),—SO₂(CH₂)_(m)P(O)(OH)₂, —SO₂NR²³R²⁵, —NR²³R²⁴, —NR²³ SO₂R²⁵; either R²¹and R²² are independently hydrogen or C₁-C₆ alkyl, or R²¹ and R²²together form an oxo group; R²³ is hydrogen or C₁-C₆ alkyl; R²⁴ is—SO₂R²⁵ or —C(O)R²⁵; or R²³ and R²⁴ together with the nitrogen to whichthey are attached form a substituted or unsubstituted heterocyclic ring;R²⁵ is C₁-C₆ alkyl; and m is 1, 2, 3, or 4. In some embodiments, R¹ isan aryl. In some embodiments, the aryl is a phenyl.

In some embodiments, any of the siNA molecules, sense strands, firstnucleotide sequences, antisense strands, or second nucleotide sequencesdisclosed herein comprise a 5′-stabilized end cap of Formula (Ib):

wherein R¹ is H, a nucleobase, aryl, or heteroaryl; R² is

—CH═CD-Z, —CD=CH—Z, —CD=CD-Z, —(CR²¹R²²)_(n)—Z, or —(C₂-C₆ alkenylene)-Zand R²⁰ is H; or R² and R²⁰ together form a 3- to 7-membered carbocyclicring substituted with —(CR²¹R²²)_(n)—Z or —(C₂-C₆ alkenylene)-Z; n is 1,2, 3, or 4; Z is —ONR²³R²⁴, —OP(O)OH(CH₂)_(m)CO₂R²³,—OP(S)OH(CH₂)_(m)CO₂R²³, —P(O)(OH)₂, —P(O)(OH)(OCH₃), —P(O)(OH)(OCD₃),—SO₂(CH₂)_(m)P(O)(OH)₂, —SO₂NR²³R²⁵, —NR²³R²⁴, —NR²³SO₂R²⁵; either R²¹and R²² are independently hydrogen or C₁-C₆ alkyl, or R²¹ and R²²together form an oxo group; R²³ is hydrogen or C₁-C₆ alkyl; R²⁴ is—SO₂R²⁵ or —C(O)R²⁵; or R²³ and R²⁴ together with the nitrogen to whichthey are attached form a substituted or unsubstituted heterocyclic ring;R²⁵ is C₁-C₆ alkyl; and m is 1, 2, 3, or 4. In some embodiments, R¹ isan aryl. In some embodiments, the aryl is a phenyl.

In some embodiments, any of the siNA molecules, sense strands, firstnucleotide sequences, antisense strands, or second nucleotide sequencesdisclosed herein comprise a 5′-stabilized end cap of Formula (Ic):

wherein R¹ is a nucleobase, aryl, heteroaryl, or H,

R² is

—CH═CD-Z, —CD=CH—Z, —CD=CD-Z, —(CR²¹R²²)_(n)—Z, or —(C₂-C₆ alkenylene)-Zand R²⁰ is hydrogen; or R² and R²⁰ together form a 3- to 7-memberedcarbocyclic ring substituted with —(CR²¹R²²)_(n)—Z or —(C₂-C₆alkenylene)-Z; n is 1, 2, 3, or 4; Z is —ONR²³R²⁴,—OP(O)OH(CH₂)_(m)CO₂R²³, —OP(S)OH(CH₂)_(m)CO₂R²³, —P(O)(OH)₂,—P(O)(OH)(OCH₃), —P(O)(OH)(OCD₃), —SO₂(CH₂)_(m)P(O)(OH)₂, —SO₂NR²³R²⁵,—NR²³R²⁴, or —NR²³SO₂R²⁵; R²¹ and R²² either are independently hydrogenor C₁-C₆ alkyl, or R²¹ and R²² together form an oxo group; R²³ ishydrogen or C₁-C₆ alkyl; R²⁴ is —SO₂R²⁵ or —C(O)R²⁵; or

R²³ and R²⁴ together with the nitrogen to which they are attached form asubstituted or unsubstituted heterocyclic ring; R²⁵ is C₁-C₆ alkyl; andm is 1, 2, 3, or 4. In some embodiments, R¹ is an aryl. In someembodiments, the aryl is a phenyl.

In some embodiments, any of the siNA molecules, sense strands, firstnucleotide sequences, antisense strands, or second nucleotide sequencesdisclosed herein comprise a 5′-stabilized end cap of Formula (IIa):

wherein R¹ is a nucleobase, aryl, heteroaryl,

or H, R² is

—CH₂SO₂NHCH₃, or

R⁹ is —SO₂CH₃ or —COCH₃,

is a double or single bond, R¹⁰=—CH₂PO₃H or —NHCH₃, R¹¹ is —CH₂— or—CO—, and R¹² is H and R¹¹ is CH₃ or R¹² and R¹¹ together form—CH₂CH₂CH₂—. In some embodiments, le is an aryl. In some embodiments,the aryl is a phenyl.

In some embodiments, any of the siNA molecules, sense strands, firstnucleotide sequences, antisense strands, or second nucleotide sequencesdisclosed herein comprise a 5′-stabilized end cap of Formula (IIb):

wherein R¹ is a nucleobase, aryl, heteroaryl, or H, R² is

—CH₂SO₂NHCH₃, or

R⁹ is —SO₂CH₃ or —COCH₃,

is a double or single bond, R¹⁰=—CH₂PO₃H or —NHCH₃, is —CH₂— or —CO—,and R¹² is H and R¹³ is CH₃ or R¹² and R¹³ together form —CH₂CH₂CH₂—. Insome embodiments, le is an aryl. In some embodiments, the aryl is aphenyl.

In some embodiments, any of the siNA molecules, sense strands, firstnucleotide sequences, antisense strands, or second nucleotide sequencesdisclosed herein comprise a 5′-stabilized end cap of Formula (III):

wherein R¹ is a nucleobase, aryl, heteroaryl, or H, L is —CH₂—, —CH═CH—,—CO—, or —CH₂CH₂—, and A is —ONHCOCH₃, —ONHSO₂CH₃, —PO₃H,—OP(SOH)CH₂CO₂H, —SO₂CH₂PO₃H, —SO₂NHCH₃, —NHSO₂CH₃, or —N(SO₂CH₂CH₂CH₂).In some embodiments, R¹ is an aryl. In some embodiments, the aryl is aphenyl.

In some embodiments, any of the siNA molecules, sense strands, firstnucleotide sequences, antisense strands, or second nucleotide sequencesdisclosed herein comprise a 5′-stabilized end cap selected from Examples5-11, 33-35, 38, 39, 43, and 49-53 5′ end cap monomers.

Further disclosed herein are siNA molecules comprising (a) a5′-stabilized end cap of Formula (Ia):

wherein R¹ is a nucleobase, aryl, heteroaryl, or H; R² is

—CH═CD-Z, —CD=CH—Z, —CD=CD-Z, —(CR²¹R²²)_(n)—Z, or —(C₂-C₆ alkenylene)-Zand R²⁰ is H; or R² and R²⁰ together form a 3- to 7-membered carbocyclicring substituted with —(CR²¹R²²)_(n)—Z or —(C₂-C₆ alkenylene)-Z; n is 1,2, 3, or 4; Z is —ONR²³R²⁴, —OP(O)OH(CH₂)_(m)CO₂R²³,—OP(S)OH(CH₂)_(m)CO₂R²³, —P(O)(OH)₂, —P(O)(OH)(OCH₃), —P(O)(OH)(OCD₃),—SO₂(CH₂)_(m)P(O)(OH)₂, —SO₂NR²³R²⁵, —NR²³R²⁴, —NR²³SO₂R²⁵; either R²¹and R²² are independently hydrogen or C₁-C₆ alkyl, or R²¹ and R²²together form an oxo group; R²³ is hydrogen or C₁-C₆ alkyl; R²⁴ is—SO₂R²⁵ or —C(O)R²⁵; or R²³ and R²⁴ together with the nitrogen to whichthey are attached form a substituted or unsubstituted heterocyclic ring;R²⁵ is C₁-C₆ alkyl; and m is 1, 2, 3, or 4; and (b) a short interferingnucleic acid (siNA), wherein the 5′-stabilized end cap is conjugated tothe siNA. In some embodiments, R¹ is an aryl. In some embodiments, thearyl is a phenyl.

Further disclosed herein are siNA molecules comprising (a) a5′-stabilized end cap of Formula (Ib):

wherein R¹ is a nucleobase, aryl, heteroaryl, or H; R² is

—CH═CD-Z, —CD=CH—Z, —CD=CD-Z, —(CR²¹R²²)_(n)—Z, or —(C₂-C₆ alkenylene)-Zand R²⁰ is H; or R² and R²⁰ together form a 3- to 7-membered carbocyclicring substituted with —(CR²¹R²²)_(n)—Z or —(C₂-C₆ alkenylene)-Z; n is 1,2, 3, or 4; Z is —ONR²³R²⁴, —OP(O)OH(CH₂)_(m)CO₂R²³,—OP(S)OH(CH₂)_(m)CO₂R²³, —P(O)(OH)₂, —P(O)(OH)(OCH₃), —P(O)(OH)(OCD₃),—SO₂(CH₂)_(m)P(O)(OH)₂, —SO₂NR²³R²⁵, —NR²³R²⁴, —NR²³SO₂R²⁵; either R²¹and R²² are independently hydrogen or C₁-C₆ alkyl, or R²¹ and R²²together form an oxo group; R²³ is hydrogen or C₁-C₆ alkyl; R²⁴ is—SO₂R²⁵ or —C(O)R²⁵; or R²³ and R²⁴ together with the nitrogen to whichthey are attached form a substituted or unsubstituted heterocyclic ring;R²⁵ is C₁-C₆ alkyl; and m is 1, 2, 3, or 4; and (b) a short interferingnucleic acid (siNA), wherein the 5′-stabilized end cap is conjugated tothe siNA. In some embodiments, R¹ is an aryl. In some embodiments, thearyl is a phenyl.

Further disclosed herein are siNA molecules comprising (a) a5′-stabilized end cap of Formula (Ic):

wherein R¹ is a nucleobase, aryl, heteroaryl, or H, R² is

—CH═CD-Z, —CD=CH—Z, —CD=CD-Z, —(CR²¹R²²)_(n)—Z, or —(C₂-C₆ alkenylene)-Zand R²⁰ is hydrogen; or R² and R²⁰ together form a 3- to 7-memberedcarbocyclic ring substituted with —(CR²¹R²²)_(n)—Z or —(C₂-C₆alkenylene)-Z; n is 1, 2, 3, or 4; Z is —ONR²³R²⁴,—OP(O)OH(CH₂)_(m)CO₂R²³, —OP(S)OH(CH₂)_(m)CO₂R²³, —P(O)(OH)₂,—P(O)(OH)(OCH₃), —P(O)(OH)(OCD₃), —SO₂(CH₂)_(m)P(O)(OH)₂, —SO₂NR²³R²⁵,NR²³R²⁴, or —NR²³SO₂R²⁵; R²¹ and R²² either are independently hydrogenor C₁-C₆ alkyl, or R²¹ and R²² together form an oxo group; R²³ ishydrogen or C₁-C₆ alkyl; R²⁴ is —SO₂R²⁵ or —C(O)R²⁵; or R²³ and R²⁴together with the nitrogen to which they are attached form a substitutedor unsubstituted heterocyclic ring; R²⁵ is C₁-C₆ alkyl; and m is 1, 2,3, or 4; and (b) a short interfering nucleic acid (siNA), wherein the5′-stabilized end cap is conjugated to the siNA. In some embodiments, R¹is an aryl. In some embodiments, the aryl is a phenyl.

In some embodiments, a siNA molecule comprises (a) a 5′-stabilized endcap of Formula (IIa):

wherein R¹ is a nucleobase, aryl, heteroaryl, or H, R² is

CH₂SO₂NHCH₃, or

R⁹ is —SO₂CH₃ or —COCH₃, wherein

is a double or single bond, R¹⁰=—CH₂PO₃H or —NHCH₃, R¹¹ is —CH₂— or—CO—, and R¹² is H and R¹³ is CH₃ or R¹² and R¹³ together form—CH₂CH₂CH₂—; and (b) a short interfering nucleic acid (siNA), whereinthe 5′-stabilized end cap is conjugated to the siNA. In someembodiments, R¹ is an aryl. In some embodiments, the aryl is a phenyl.

In some embodiments, a siNA molecule comprises (a) a 5′-stabilized endcap of Formula (IIb):

wherein R¹ is a nucleobase, aryl, heteroaryl, or H, R² is

CH₂SO₂NHCH₃, or

R⁹ is —SO₂CH₃ or —COCH₃, wherein

is a double or single bond, R¹⁰=—CH₂PO₃H or —NHCH₃, R¹¹ is —CH₂— or—CO—, and R¹² is H and R¹³ is CH₃ or R¹² and R¹³ together form—CH₂CH₂CH₂—; and (b) a short interfering nucleic acid (siNA), whereinthe 5′-stabilized end cap is conjugated to the siNA. In someembodiments, R¹ is an aryl. In some embodiments, the aryl is a phenyl.

In some embodiments, a siNA molecule comprises (a) a 5′-stabilized endcap of Formula (III):

wherein R¹ is a nucleobase, aryl, heteroaryl, or H, L is —CH₂—, —CH═CH—,—CO—, or —CH₂CH₂—, and A is —ONHCOCH₃, —ONHSO₂CH₃, —PO₃H,—OP(SOH)CH₂CO₂H, —SO₂CH₂PO₃H, —SO₂NHCH₃, —NHSO₂CH₃, or —N(SO₂CH₂CH₂CH₂);and (b) a siNA, wherein the 5′-stabilized end cap is conjugated to thesiNA. In some embodiments, 10 is an aryl. In some embodiments, the arylis phenyl.

In some embodiments, any of the siNA molecules disclosed herein comprisea 5′-stabilized end cap selected from the group consisting of Formula(1) to Formula (15), Formula (9X) to Formula (12X), and Formula (9Y) toFormula (12Y):

wherein R¹ is a nucleobase, aryl, heteroaryl, or H. In some embodiments,R¹ is an aryl. In some embodiments, the aryl is a phenyl.

In some embodiments, any of the siNA molecules disclosed herein comprisea 5′-stabilized end cap selected from the group consisting of Formulas(1A)-(15A), Formulas (9B)-(12B), Formulas (9AX)-(12AX), Formulas(9AY)-(12AY), Formulas (9BX)-(12BX), and Formulas (9BY)-(12BY):

In some embodiments, any of the siNA molecules disclosed herein comprisea 5′-stabilized end cap selected from the group consisting of Formula(21) to Formula (35):

wherein R¹ is a nucleobase, aryl, heteroaryl, or H. In some embodiments,R¹ is an aryl. In some embodiments, the aryl is a phenyl.

In some embodiments, any of the siNA molecules disclosed herein comprisea 5′-stabilized end cap selected from the group consisting of Formulas(21A)-(35A), Formulas (29B)-(32B), Formulas (29AX)-(32AX), Formulas(29AY)-(32AY), Formulas (29BX)-(32BX), and Formulas (29BY)-(32BY):

In some embodiments, the 5′-stabilized end cap is attached to the 5′ endof the antisense strand. In some embodiments, the 5′-stabilized end capis attached to the 5′ end of the antisense strand via 1, 2, 3, 4, or 5or more linkers. In some embodiments, one or more linkers areindependently selected from the group consisting of a phosphodiester (por po) linker, phosphorothioate (ps) linker, phosphoramidite (HEG)linker, triethylene glycol (TEG) linker, and/or phosphorodithioatelinker.

Linkers

In some embodiments, any of the siRNAs, sense strands, first nucleotidesequences, antisense strands, and/or second nucleotide sequencesdisclosed herein comprise 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14,15, 16, 17, 18, 19, 20, 21, 22, 23 or more internucleoside linkers. Insome embodiments, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10 or more internucleosidelinkers are independently selected from the group consisting of aphosphodiester (p or po) linker, phosphorothioate (ps) linker, orphosphorodithioate linker.

In some embodiments, any of the siRNAs, sense strands, first nucleotidesequences, antisense strands, and/or second nucleotide sequencesdisclosed herein further comprise 1, 2, 3, 4 or more linkers that attacha conjugated moiety, phosphorylation blocker, and/or 5′ end cap to thesiRNA, sense strand, first nucleotide sequence, antisense strand, and/orsecond nucleotide sequences. In some embodiments, the 1, 2, 3, 4 or morelinkers are independently selected from the group consisting of aphosphodiester (p or po) linker, phosphorothioate (ps) linker,phosphoramidite (HEG) linker, triethylene glycol (TEG) linker, and/orphosphorodithioate linker. In some embodiments, the one or more linkersare independently selected from the group consisting of p-(ps)₂,(ps)2-p-TEG-p, (ps)2-p-HEG-p, and (ps)2-p-(HEG-p)2.

Specific Embodiments

The present disclosure provides numerous siNA that can be used to treator prevent viral infections, specifically coronavirus (e.g., SARS-CoV-2)infections, such as COVID-19. Table 3, below, provides a non-limitinglist of siNA that incorporate the nucleic acid sequences, modifiednucleotides, phosphorylation blockers, 5′ stabilized end caps, and/orlinkers of the foregoing sections. Those of skill in the art willunderstand that other exemplary siNA can be constructed by combining thesequences disclosed in Table 1 (or fragments of the sequences disclosedin Table 2) with the modified nucleotides, phosphorylation blockers, 5′stabilized end caps, and/or linkers of the foregoing sections.

TABLE 3 Exemplary siNA SEQ SEQ ID ID Name NO: Sense Sequence (5′→3′) NO:Antisense Sequence (5′→3′) ds- 4383 rGrCrUrCrCrUrArArUrUrArCrArCrUr 4605rGrUrUrGrArGrUrGrUrArArUrUrArGr siNA- CrArArCTT GrArGrCTT 001 ds- 4384rGrGrArUrGrArGrGrArArGrGrCrArAr 4606 rUrArArArUrUrGrCrCrUrUrCrCrUrCrsiNA- UrUrUrATT ArUrCrCTT 002 ds- 4385 rCrCrGrCrUrGrGrArGrArGrCrArArCr4607 rUrGrCrArGrUrUrGrCrUrCrUrCrCrUr siNA- UrGrCrATT GrCrGrGTT 003 ds-4386 rGrCrUrArUrGrArArArCrGrArUrArUr 4608rGrCrCrCrArUrArUrCrGrUrUrUrCrAr siNA- GrGrGrCTT UrArGrCTT 004 ds- 4387fUpsmApsfGmCfAmGfCmAfUmUfA 4609 mCpsfApsmGfGmAfUmGfGmUfAmAf siNA-mCfCmAfUmCfCmUfGpsTpsT UmGfCmUfGmCfUmATpsT 005 ds- 4388mCpsfApsmAmCmAmCmGmGmAmC 4610 mUpsmApsfCmGmGmUfUfUfCmGmU siNA-mGmAmAfAmCmCmGmUmApsTpsT fCmCmGmUmGfUmUmGTpsT 006 ds- 4389mCpsmApsfCmGmUmCfCfAfAmCmU 4611 mGpsfCpsmAmAmAmCmUmGmAmG siNA-fCmAmGmUmUfUmGmCTpsT mUmUmGfGmAmCmGmUmGpsTpsT 007 ds- 4390mUpsmGpsfAmAmCmAfGfCfCmCm 4612 mGpsfApsmAmCmAmCmAmUmAmG siNA-UfAmUmGmUmGfUmUmCTpsT mGmGmCfUmGmUmUmCmApsTpsT 008 ds- 4391mApsmCpsfGmAmGmCfUfUfGmGm 4613 mGpsfGpsmAmUmCmAmGmUmGmC siNA-CfAmCmUmGmAfUmCmCTpsT mCmAmAfGmCmUmCmGmUpsTpsT 009 ds- 4392mUpsmCpsfAmUmGmUfGfGfUmAm 4614 mApsfApsmCmCmAmAmCmAmCmU siNA-GfUmGmUmUmGfGmUmUTpsT mAmCmCfAmCmAmUmGmApsTpsT 010 ds- 4393mApsmCpsfAmAmCmAfUfUfAmUm 4615 mGpsfCpsmAmUmUmGmUmUmGmA siNA-CfAmAmCmAmAfUmGmCTpsT mUmAmAfUmGmUmUmGmUpsTpsT 011 ds- 4394mApsfApsmAmCmCmUmAmCmAmA 4616 mGpsmGpsfAmAmCmCfAfCfCmUmU siNA-mGmGmUfGmGmUmUmCmCpsTpsT fGmUmAmGmGfUmUmUTpsT 012 ds- 4395mCpsmGpsfUmUmUmUfUfAfAmAm 4617 mGpsfCpsmAmAmAmCmCmCmGmU siNA-CfGmGmGmUmUfUmGmCTpsT mUmUmAfAmAmAmAmCmGpsTpsT 013 ds- 4396mGpsfUpsmGmCmCmGmCmAmCmG 4618 mGpsmUpsfCmUmUmAfCfAfCmCmG siNA-mGmUmGfUmAmAmGmAmCpsTpsT fUmGmCmGmGfCmAmCTpsT 014 ds- 4397TmUpsfGpsmAmCmGmUmGmAmUm 4619 mUpsmApsfCmCmAmCfAfUfAmUmA siNA-AmUmAmUfGmUmGmGmUmApsTps fUmCmAmCmGfUmCmATpsT 015 ds- 4398mGpsmGpsfAmUmGmUfAfAfAmCm 4620 mGpsfCpsmUmAmUmGmUmAmAmG siNA-UfUmAmCmAmUfAmGmCTpsT mUmUmUfAmCmAmUmCmCpsTpsT 016 ds- 4399mApsfCpsmCmGmGmGmUmUmUmG 4621 mUpsmCpsfAmAmAmCfUfGfUmCmA siNA-mAmCmAfGmUmUmUmGmApsTpsT fAmAmCmCmCfGmGmUTpsT 017 ds- 4400mUpsmGpsfUmCmAmAfAfCfCmCm 4622 mApsfApsmAmAmUmUmAmCmCmG siNA-GfGmUmAmAmUfUmUmUTpsT mGmGmUfUmUmGmAmCmApsTpsT 018 ds- 4401mUpsmApsfAmGmUmAfUfGfCmCm 4623 mUpsfGpsmCmAmCmUmAmAmUmG siNA-AfUmUmAmGmUfGmCmATpsT mGmCmAfUmAmCmUmUmApsTpsT 019 ds- 4402mUpsmGpsfCmCmAmUfUfAfGmUm 4624 mApsfUpsmUmCmUmUmUmGmCmA siNA-GfCmAmAmAmGfAmAmUTpsT mCmUmAfAmUmGmGmCmApsTpsT 020 ds- 4403mGpsfCpsmGmAmGmCmUmCmUmA 4625 mUpsmGpsfCmAmAmAfGfAfAmUmA siNA-mUmUmCfUmUmUmGmCmApsTpsT fGmAmGmCmUfCmGmCTpsT 021 ds- 4404mGpsfApsmCmAmCmCmAmGmCmU 4626 mUpsmCpsfGmCmAmCfCfGfUmAmG siNA-mAmCmGfGmUmGmCmGmApsTpsT fCmUmGmGmUfGmUmCTpsT 022 ds- 4405mCpsmApsfAmUmAmGfCfCfGmCmC 4627 mCpsfCpsmUmCmUmAmGmUmGmG siNA-fAmCmUmAmGfAmGmGTpsT mCmGmGfCmUmAmUmUmGpsTpsT 023 ds- 4406mApsmCpsfUmGmCmUfUfAfUmGm 4628 mCpsfApsmCmUmAmUmUmAmGmC siNA-CfUmAmAmUmAfGmUmGTpsT mAmUmAfAmGmCmAmGmUpsTpsT 024 ds- 4407mApsfCpsmAmUmCmAmGmCmAmU 4629 mApsmUpsfCmAmGmGfAfGfUmAmU siNA-mAmCmUfCmCmUmGmAmUpsTpsT fGmCmUmGmAfUmGmUTpsT 025 ds- 4408mUpsmApsfGmGmAmGfGfUfAmUm 4630 mUpsfApsmAmUmAmGmCmUmCmA siNA-GfAmGmCmUmAfUmUmATpsT mUmAmCfCmUmCmCmUmApsTpsT 026 ds- 4409mApsmCpsfUmAmUmGfGfUfGmAm 4631 mApsfCpsmAmAmCmAmGmCmAmU siNA-UfGmCmUmGmUfUmGmUTpsT mCmAmCfCmAmUmAmGmUpsTpsT 027 ds- 4410mApsfCpsmAmUmAmGmUmGmCmU 4632 mUpsmGpsfCmCmAmCfAfAfGmAmG siNA-mCmUmUfGmUmGmGmCmApsTpsT fCmAmCmUmAfUmGmUTpsT 028 ds- 4411mUpsfApsmUmAmCmAmCmUmAmU 4633 mUpsmCpsfUmGmCmUfCfGfCmAmU siNA-mGmCmGfAmGmCmAmGmApsTpsT fAmGmUmGmUfAmUmATpsT 029 ds- 4412mApsmApsfUmUmCmAfAfAfGmUm 4634 mGpsfUpsmUmGmAmAmUmUmCmA siNA-GfAmAmUmUmCfAmAmCTpsT mCmUmUfUmGmAmAmUmUpsTpsT 030 ds- 4413mApsfGpsmGmAmAmCmAmUmGm 4635 mUpsmApsfGmGmUmCfCfAfGmAmC siNA-UmCmUmGfGmAmCmCmUmApsTps fAmUmGmUmUfCmCmUTpsT 031 T ds- 4414mUpsfGpsmAmAmUmAmUmGmAm 4636 mUpsmApsfUmGmAmCfUfAfUmGmU siNA-CmAmUmAfGmUmCmAmUmApsTps fCmAmUmAmUfUmCmATpsT 032 T ds- 4415mUpsmUpsfUmGmAmGfCfUfUmUm 4637 mGpsfCpsmUmUmAmGmCmCmCmA siNA-GfGmGmCmUmAfAmGmCTpsT mAmAmGfCmUmCmAmAmApsTpsT 033 ds- 4416mUpsmApsfAmUmGmAfUfGfAmAm 4638 mUpsfUpsmUmGmCmGmAmCmAmU siNA-UfGmUmCmGmCfAmAmATpsT mUmCmAfUmCmAmUmUmApsTpsT 034 ds- 4417mGpsmApsfGmUmAmCfGfAfAmCm 4639 mApsfGpsmUmAmCmAmUmAmAmG siNA-UfUmAmUmGmUfAmCmUTpsT mUmUmCfGmUmAmCmUmCpsTpsT 035 ds- 4418mGpsmGpsfUmAmCmGfUfUfAmAm 4640 mUpsfApsmUmUmAmAmCmUmAmU siNA-UfAmGmUmUmAfAmUmATpsT mUmAmAfCmGmUmAmCmCpsTpsT 036 ds- 4419mGpsfApsmAmAmAmAmGmAmAm 4641 mApsmApsfUmAmGmCfGfUfAmCmU siNA-GmUmAmCfGmCmUmAmUmUpsTps fUmCmUmUmUfUmUmCTpsT 037 T ds- 4420mGpsfCpsmAmAmGmAmAmUmAmC 4642 mGpsmCpsfUmUmUmCfGfUfGmGmU siNA-mCmAmCfGmAmAmAmGmCpsTpsT fAmUmUmCmUfUmGmCTpsT 038 ds- 4421mApsfCpsmAmAmUmCmGmAmAmG 4643 mCpsmUpsfUmAmCmUfGfCfGmCmU siNA-mCmGmCfAmGmUmAmAmGpsTpsT fUmCmGmAmUfUmGmUTpsT 039 ds- 4422mUpsmUpsfCmUmGmGfUfCfUmAm 4644 mUpsfApsmGmUmUmCmGmUmUmU siNA-AfAmCmGmAmAfCmUmATpsT mAmGmAfCmCmAmGmAmApsTpsT 040 ds- 4423mUpsfApsmAmUmAmAmGmAmAm 4645 mCpsmApsfCmGmAmAfCfGfCmUmU siNA-AmGmCmGfUmUmCmGmUmGpsTps fUmCmUmUmAfUmUmATpsT 041 T ds- 4424mUpsfGpsmUmAmUmGmCmAmGmC 4646 mUpsmCpsfAmGmGmUfUfUfUmGmC siNA-mAmAmAfAmCmCmUmGmApsTpsT fUmGmCmAmUfAmCmATpsT 042 ds- 4425mCpsfApsmUmCmUmGmUmUmGmU 4647 mCpsmApsfGmUmAmAfGfUfGmAmC siNA-mCmAmCfUmUmAmCmUmGpsTpsT fAmAmCmAmGfAmUmGTpsT 043 ds- 4426mUpsmApsfCmCmCmAfAfUfAmAm 4648 mGpsfApsmCmGmCmAmGmUmAmU siNA-UfAmCmUmGmCfGmUmCTpsT mUmAmUfUmGmGmGmUmApsTpsT 044 ds- 4427mCpsfUpsmUmCmGmGmUmAmGmU 4649 mApsmApsfAmUmUmGfGfCfUmAmC siNA-mAmGmCfCmAmAmUmUmUpsTpsT fUmAmCmCmGfAmAmGTpsT 045 ds- 4428mCpsmApsfAmAmAmGfGfCfUmUm 4650 mUpsfCpsmUmGmCmGmUmAmGmA siNA-CfUmAmCmGmCfAmGmATpsT mAmGmCfCmUmUmUmUmGpsTpsT 046 ds- 4429mUpsmGpsfUmCmAmCfUfAfAmGm 4651 mApsfGpsmCmAmGmAmUmUmUmC siNA-AfAmAmUmCmUfGmCmUTpsT mUmUmAfGmUmGmAmCmApsTpsT 047 ds- 4430mGpsmApsfCmAmAmGfGfAfAmCm 4652 mUpsfUpsmGmUmAmAmUmCmAmG siNA-UfGmAmUmUmAfCmAmATpsT mUmUmCfCmUmUmGmUmCpsTpsT 048 ds- 4431mCpsmApsfUmGmGmAfAfGfUmCm 4653 mCpsfGpsmAmAmGmGmUmGmUmG siNA-AfCmAmCmCmUfUmCmGTpsT mAmCmUfUmCmCmAmUmGpsTpsT 049 ds- 4432mCpsfApsmUmUmCmUmGmCmAmC 4654 mUpsmCpsfUmAmCmUfCfUfUmGmU siNA-mAmAmGfAmGmUmAmGmApsTpsT fGmCmAmGmAfAmUmGTpsT 050 ds- 4433mCpsmApsfCmAmUmAfGfCfAmAm 4655 mGpsfApsmUmUmAmAmAmGmAmU siNA-UfCmUmUmUmAfAmUmCTpsT mUmGmCfUmAmUmGmUmGpsTpsT 051 ds- 4434mApsfApsmAmUmGmUmGmGmUm 4656 mUpsmGpsfAmAmAmGfAfGfCmCmA siNA-GmGmCmUfCmUmUmUmCmApsTps fCmCmAmCmAfUmUmUTpsT 052 T ds- 4435mUpsfUpsmUmAmCmAmCmAmUmU 4657 mApsmApsfGmAmGmCfCfCfUmAmA siNA-mAmGmGfGmCmUmCmUmUpsTpsT fUmGmUmGmUfAmAmATpsT 053 ds- 4436mUpsmApsmCmGfGmUmUmUfCfGf 4658 mUpsfGpsmCmAmAmCmAmCmGmG siNA-UmCmCfGmUmGmUmUfGmCpsmA mAmCmGfAmAmAmCmCmGmUmAp 054 sTpsT ds- 4437mApsfApsmCmUmGmAmGmUmUm 4659 mApsmApsmAmCfAmCmAmCfGfUfC siNA-GmGmAmCfGmUmGmUmGmUmUm mCmAfAmCmUmCmAfGmUpsmU 055 UpsTpsT ds- 4438mUpsmGpsmAmAfCmAmGmCfCfCf 4660 mApsfUpsmGmAmAmCmAmCmAmU siNA-UmAmUfGmUmGmUmUfCmApsmU mAmGmGfGmCmUmGmUmUmCmAp 056 sTpsT ds- 4439mUpsmApsmUmUfUmAmAmAfAfCf 4661 mApsfUpsmUmGmUmCmAmGmUmA siNA-UmUmAfCmUmGmAmCfAmApsmU mAmGmUfUmUmUmAmAmAmUmA 057 psTpsT ds- 4440mUpsfUpsmUmUmCmCmAmCmUmA 4662 mCpsmUpsmCmUfGmAmAmGfAfAfG siNA-mCmUmUfCmUmUmCmAmGmAmG mUmAfGmUmGmGmAfAmApsmA 058 psTpsT ds- 4441mUpsfGpsmUmUmAmAmAmAmCmC 4663 mGpsmUpsmGmGfUmAmGmUfGfUf siNA-mAmAmCfAmCmUmAmCmCmAmC UmGmGfUmUmUmUmAfAmCpsmA 059 psTpsT ds- 4442mGpsfUpsmAmAmCmAmAmAmCmC 4664 mApsmCpsmCmAfCmCmUmUfGfUfA siNA-mUmAmCfAmAmGmGmUmGmGmU mGmGfUmUmUmGmUfUmApsmC 060 psTpsT ds- 4443mUpsmGpsmUmUfGmUmGmUfAfCf 4665 mUpsfApsmCmCmAmGmUmGmUmG siNA-AmCmAfCmAmCmUmGfGmUpsmA mUmGmUfAmCmAmCmAmAmCmAp 061 sTpsT ds- 4444mApsmApsmAmGfGmUmUmAfUfGf 4666 mApsfCpsmAmAmCmUmAmCmAmG siNA-GmCmUfGmUmAmGmUfUmGpsmU mCmCmAfUmAmAmCmCmUmUmUp 062 sTpsT ds- 4445mUpsfUpsmAmCmAmCmCmGmCmA 4667 mUpsmUpsmAmAfAmCmGmGfGfUfU siNA-mAmAmCfCmCmGmUmUmUmAmA mUmGfCmGmGmUmGfUmApsmA 063 psTpsT ds- 4446mGpsmUpsmGmUfAmAmGmUfGfCf 4668 mUpsfApsmAmGmAmCmGmGmGmC siNA-AmGmCfCmCmGmUmCfUmUpsmA mUmGmCfAmCmUmUmAmCmAmCp 064 sTpsT ds- 4447mApsmCpsmAmUfGmGmUmAfCfCf 4669 mGpsfUpsmGmAmUmAmUmAmUmG siNA-AmCmAfUmAmUmAmUfCmApsmC mUmGmGfUmAmCmCmAmUmGmUp 065 sTpsT ds- 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4583mApsfApsmGfUmCfAmAfCmAfCmCf 4805 fUpsmUpsfGmUfUmAfAmUfGmGfUm siNA-AmUfUmAfAmCfAmApsTpsT GfUmUfGmAfCmUfUTpsT 201 ds- 4584mUpsfCpsmAfAmCfUmGfUmUfGmCf 4806 fUpsmUpsfAmCfUmUfUmUfGmCfAm siNA-AmAfAmAfGmUfAmApsTpsT AfCmAfGmUfUmGfATpsT 202 ds- 4585mUpsfCpsmAfUmAfAmCfAmAfAmCf 4807 fApsmUpsfGmCfUmGfGmUfGmUfUm siNA-AmCfCmAfGmCfAmUpsTpsT UfGmUfUmAfUmGfATpsT 203 ds- 4586mGpsfUpsmAfGmUfUmGfCmAfUmC 4808 fCpsmUpsfUmCfUmGfGmUfGmAfUm siNA-fAmCfCmAfGmAfAmGpsTpsT GfCmAfAmCfUmAfCTpsT 204 ds- 4587fUpsmGpsfCmUfCmAfCmAfGmCfAm 4809 mGpsfCpsmAfUmAfGmUfGmUfGmCf siNA-CfAmCfUmAfUmGfCTpsT UmGfUmGfAmGfCmApsTpsT 205 ds- 4588fApsmGpsfAmUfGmCfGmGfUmGfA 4810 mGpsfUpsmAfAmAfCmAfAmUfCmAf siNA-mUfUmGfUmUfUmAfCTpsT CmCfGmCfAmUfCmUpsTpsT 206 ds- 4589mApsfUpsmCfUmAfCmUfUmUfCmUf 4811 fUpsmGpsfUmGfUmUfUmGfAmGfAm siNA-CmAfAmAfCmAfCmApsTpsT AfAmGfUmAfGmAfUTpsT 207 ds- 4590fUpsmUpsfUmAfAmUfGmUfUmAfG 4812 mApsfApsmGfCmAfUmCfAmCfUmAf siNA-mUfGmAfUmGfCmUfUTpsT AmCfAmUfUmAfAmApsTpsT 208 ds- 4591fApsmCpsfUmAfAmAfCmUfUmCfCm 4813 mCpsfGpsmUfAmAfUmAfAmGfGmAf siNA-UfUmAfUmUfAmCfGTpsT AmGfUmUfUmAfGmUpsTpsT 209 ds- 4592mUpsfUpsmUfGmUfAmAfUmCfAmG 4814 fApsmGpsfAmCfAmAfGmGfAmAfCm siNA-fUmUfCmCfUmUfGmUfCmUpsTpsT UfGmAfUmUfAmCfAmAfATpsT 210 ds- 4593fCpsmUpsfUmAfCmUfGmCfGmCfUm 4815 mApsfCpsmAfAmUfCmGfAmAfGmCf siNA-UfCmGfAmUfUmGfUTpsT GmCfAmGfUmAfAmGpsTpsT 211 ds- 4594mApsfCpsmAfCmUfAmUfUmAfGmCf 4816 fApsmApsfCmUfGmCfUmUfAmUfGm siNA-AmUfAmAfGmCfAmGfUmUpsTpsT CfUmAfAmUfAmGfUmGfUTpsT 212 ds- 4595mApsfGpsmAfAmUfAmCfCmAfCmGf 4817 fUpsmUpsfCmUfUmGfCmUfUmUfCm siNA-AmAfAmGfCmAfAmGfAmApsTpsT GfUmGfGmUfAmUfUmCfUTpsT 213 ds- 4596mApsfCpsmAfCmAfAmUfCmGfAmAf 4818 fCpsmUpsfUmAfCmUfGmCfGmCfUm siNA-GmCfGmCfAmGfUmAfAmGpsTpsT UfCmGfAmUfUmGfUmGfUTpsT 214 ds- 4597fCpsmUpsfAmCfUmCfUmUfGmUfGm 4819 mApsfUpsmUfCmAfUmUfCmUfGmCf siNA-CfAmGfAmAfUmGfAmAfUTpsT AmCfAmAfGmAfGmUfAmGpsTpsT 215 ds- 4598fUpsmUpsfUmCfUmCfAmAfCmUfAm 4820 mApsfGpsmGfAmAfGmUfUmUfAmGf siNA-AfAmCfUmUfCmCfUpsTpsT UmUfGmAfGmAfAmApsTpsT 216 ds- 4599mApsmGpsmAmCfAmAmGmGfAfAf 4821 vmUpsfUpsmUmGmUmAmAmUmCm siNA-CmUmGfAmUmUmAmCfAmAmA AmGmUmUfCmCmUmUmGmUmCm 217 UpsTpsT ds- 4600mApsmGpsmAmCmAmAfGmGfAfAf 4822 vmUpsfUpsmUmGmUfAmAmUmCmA siNA-CmUmGmAmUmUmAmCmAmAmA mGmUmUfCmCfUmUmGmUmCmUps 218 mUpsmU ds- 4601mApsmGpsmAmCmAmAfGmGfAfAf 4823 vmUpsfUpsmUmGfUmAmAfUmCmA siNA-CmUmGmAmUmUmAmCmAmAmA mGmUmUfCmCmUfUmGmUfCmUps 219 mUpsmU ds- 4602fCpsmUpsfAmCfUmCfUmUfGmUfGm 4824 vmApsfUpsmUfCmAfUmUfCmUfGmC siNA-CfAmGfAmAfUmGfAmAfU fAmCfAmAfGmAfGmUfAmGpsTpsT 220 ds- 4603mCpsmUpsmAmCmUmCfUmUfGfUf 4825 vmApsfUpsmUmCmAfUmUmCmUmG siNA-GmCmAmGmAmAmUmGmAmAmU mCmAmCfAmAfGmAmGmUmAmGps 221 mUpsmU ds- 4604mCpsmUpsmAmCmUmCfUmUfGfUf 4826 vmApsfUpsmUmCfAmUmUfCmUmG siNA-GmCmAmGmAmAmUmGmAmAmU mCmAmCfAmAmGfAmGmUfAmGps 222 mUpsmU ds- 4827mApsmGpsmAmCfAmAmGmGfAfAf 4829 vmUpsfUpsmUmGmUmAmAmUmCm siNA-CmUmGfAmUmUmAmCfApsmApsm AmGmUmUfCmCmUmUmGmUmCm 223 A UpsmUpsmU ds- 4828fCpsmUpsfAmCfUmCfUmUfGmUfGm 4830  vmApsfUpsmUfCmAfUmUfCmUfGmC siNA-CfAmGfAmAfUmGfApsmApsfU fAmCfAmAfGmAfGmUfAmGpsmUps 224 mU mX= 2′-O-methyl nucleotide; fX = 2′-fluoro nucleotide; ps= phosphorothioate linkage; vX = 5′ vinyl phosphonate nucleotide; vmX= 5′ vinyl phosphonate, 2′-O-methyl nucleotide

In some embodiments, a siNA of the present disclosure may comprise asense strand selected from any one of SEQ ID NOs: 4383 to 4604, 4827,and 4828. In some embodiments, a siNA of the present disclosure maycomprise an antisense strand selected from any one of SEQ ID NOs: 4605to 4826, 4829, and 4830. In some embodiments, a siNA of the presentdisclosure may comprise a sense strand selected from any one of SEQ IDNOs: 4383 to 4604, 4827, and 4828 and an antisense strand selected fromany one of SEQ ID NOs: 4605 to 4826, 4829, and 4830. In someembodiments, a siNA of the present disclosure may comprise a sensestrand and an antisense strand, respectively, selected from SEQ ID NOs:

4383 and 4605; 4384 and 4606; 4385 and 4607; 4386 and 4608; 4387 and4609; 4388 and 4610; 4389 and 4611; 4390 and 4612; 4391 and 4613; 4392and 4614; 4393 and 4615; 4394 and 4616; 4395 and 4617; 4396 and 4618;4397 and 4619; 4398 and 4620; 4399 and 4621; 4400 and 4622; 4401 and4623; 4402 and 4624; 4403 and 4625; 4404 and 4626; 4405 and 4627; 4406and 4628; 4407 and 4629; 4408 and 4630; 4409 and 4631; 4410 and 4632;4411 and 4633; 4412 and 4634; 4413 and 4635; 4414 and 4636; 4415 and4637; 4416 and 4638; 4417 and 4639; 4418 and 4640; 4419 and 4641; 4420and 4642; 4421 and 4643; 4422 and 4644; 4423 and 4645; 4424 and 4646;4425 and 4647; 4426 and 4648; 4427 and 4649; 4428 and 4650; 4429 and4651; 4430 and 4652; 4431 and 4653; 4432 and 4654; 4433 and 4655; 4434and 4656; 4435 and 4657; 4436 and 4658; 4437 and 4659; 4438 and 4660;4439 and 4661; 4440 and 4662; 4441 and 4663; 4442 and 4664; 4443 and4665; 4444 and 4666; 4445 and 4667; 4446 and 4668; 4447 and 4669; 4448and 4670; 4449 and 4671; 4450 and 4672; 4451 and 4673; 4452 and 4674;4453 and 4675; 4454 and 4676; 4455 and 4677; 4456 and 4678; 4457 and4679; 4458 and 4680; 4459 and 4681; 4460 and 4682; 4461 and 4683; 4462and 4684; 4463 and 4685; 4464 and 4686; 4465 and 4687; 4466 and 4688;4467 and 4689; 4468 and 4690; 4469 and 4691; 4470 and 4692; 4471 and4693; 4472 and 4694; 4473 and 4695; 4474 and 4696; 4475 and 4697; 4476and 4698; 4477 and 4699; 4478 and 4700; 4479 and 4701; 4480 and 4702;4481 and 4703; 4482 and 4704; 4483 and 4705; 4484 and 4706; 4485 and4707; 4486 and 4708; 4487 and 4709; 4488 and 4710; 4489 and 4711; 4490and 4712; 4491 and 4713; 4492 and 4714; 4493 and 4715; 4494 and 4716;4495 and 4717; 4496 and 4718; 4497 and 4719; 4498 and 4720; 4499 and4721; 4500 and 4722; 4501 and 4723; 4502 and 4724; 4503 and 4725; 4504and 4726; 4505 and 4727; 4506 and 4728; 4507 and 4729; 4508 and 4730;4509 and 4731; 4510 and 4732; 4511 and 4733; 4512 and 4734; 4513 and4735; 4514 and 4736; 4515 and 4737; 4516 and 4738; 4517 and 4739; 4518and 4740; 4519 and 4741; 4520 and 4742; 4521 and 4743; 4522 and 4744;4523 and 4745; 4524 and 4746; 4525 and 4747; 4526 and 4748; 4527 and4749; 4528 and 4750; 4529 and 4751; 4530 and 4752; 4531 and 4753; 4532and 4754; 4533 and 4755; 4534 and 4756; 4535 and 4757; 4536 and 4758;4537 and 4759; 4538 and 4760; 4539 and 4761; 4540 and 4762; 4541 and4763; 4542 and 4764; 4543 and 4765; 4544 and 4766; 4545 and 4767; 4546and 4768; 4547 and 4769; 4548 and 4770; 4549 and 4771; 4550 and 4772;4551 and 4773; 4552 and 4774; 4553 and 4775; 4554 and 4776; 4555 and4777; 4556 and 4778; 4557 and 4779; 4558 and 4780; 4559 and 4781; 4560and 4782; 4561 and 4783; 4562 and 4784; 4563 and 4785; 4564 and 4786;4565 and 4787; 4566 and 4788; 4567 and 4789; 4568 and 4790; 4569 and4791; 4570 and 4792; 4571 and 4793; 4572 and 4794; 4573 and 4795; 4574and 4796; 4575 and 4797; 4576 and 4798; 4577 and 4799; 4578 and 4800;4579 and 4801; 4580 and 4802; 4581 and 4803; 4582 and 4804; 4583 and4805; 4584 and 4806; 4585 and 4807; 4586 and 4808; 4587 and 4809; 4588and 4810; 4589 and 4811; 4590 and 4812; 4591 and 4813; 4592 and 4814;4593 and 4815; 4594 and 4816; 4595 and 4817; 4596 and 4818; 4597 and4819; 4598 and 4820; 4599 and 4821; 4600 and 4822; 4601 and 4823; 4602and 4824; 4603 and 4825; 4604 and 4826; 4827 and 4829; & 4828 and 4830.

In some embodiments, the siNA can be selected from ds-siNA-196 (senseand antisense respectively comprising SEQ ID NOs: 4578 and 4800),ds-siNA-197 (sense and antisense respectively comprising SEQ ID NOs:4579 and 4801), ds-siNA-198 (sense and antisense respectively comprisingSEQ ID NOs: 4580 and 4802), ds-siNA-199 (sense and antisenserespectively comprising SEQ ID NOs: 4581 and 4803), ds-siNA-217 (senseand antisense respectively comprising SEQ ID NOs: 4599 and 4821),ds-siNA-218 (sense and antisense respectively comprising SEQ ID NOs:4600 and 4822), ds-siNA-219 (sense and antisense respectively comprisingSEQ ID NOs: 4601 and 4823), ds-siNA-220 (sense and antisenserespectively comprising SEQ ID NOs: 4602 and 4824), ds-siNA-221 (senseand antisense respectively comprising SEQ ID NOs: 4603 and 4825), andds-siNA-222 (sense and antisense respectively comprising SEQ ID NOs:4604 and 4826).

In some embodiments, the siNA can be selected from ds-siNA-196 (senseand antisense respectively comprising SEQ ID NOs: 4578 and 4800),ds-siNA-197 (sense and antisense respectively comprising SEQ ID NOs:4579 and 4801), ds-siNA-198 (sense and antisense respectively comprisingSEQ ID NOs: 4580 and 4802), and ds-siNA-199 (sense and antisenserespectively comprising SEQ ID NOs: 4581 and 4803). These siNA comprisea 5′-vinyl phosphonate and are derived from siRNAs that showed highpotency in the live virus assay prior to the incorporation of the5′-vinyl phosphonate. It was determined that the 5′-VP further improvedpotency for all constructs (see Examples). The most potent siNA wereds-siNA-196 and ds-siNA-199, which were selected for furthermodification.

In some embodiments, the siNA can be selected from, ds-siNA-217 (senseand antisense respectively comprising SEQ ID NOs: 4599 and 4821),ds-siNA-218 (sense and antisense respectively comprising SEQ ID NOs:4600 and 4822), ds-siNA-219 (sense and antisense respectively comprisingSEQ ID NOs: 4601 and 4823), ds-siNA-220 (sense and antisenserespectively comprising SEQ ID NOs: 4602 and 4824), ds-siNA-221 (senseand antisense respectively comprising SEQ ID NOs: 4603 and 4825), andds-siNA-222 (sense and antisense respectively comprising SEQ ID NOs:4604 and 4826). These siNA are further modified forms of ds-siNA-196 andds-siNA-199, which have different 2′-fluoro contents (three variants foreach one of the parent siRNAs). All of these siNA also showed highpotency across screening assays (see Examples).

Additionally, analogs of the specific embodiments (ds-siNA-001 tods-siNA-224) can be prepared by altering or adjusting the modifiednucleotides, phosphorylation blockers, 5′-stabilized end caps, and/orlinkers as disclosed herein. For example, ds-siNA-223 is an analog ofds-siNA-196 in which an additional ps and mUmU overhang have beenincorporated in place of dTdT. Similarly, ds-siNA-224 is an analog ofds-siNA-199 in which an additional ps and mUmU overhang have beenincorporated in place of dTdT. Those skilled in the art will understandthat other analogs can be similarly constructed.

Any of the foregoing specific embodiments can be incorporated into apharmaceutical compositions, either alone or in combination with 1, 2,3, 4, 5, 6, 7, 8, 9, or 10 or more additional siNA disclosed herein. Anyof the foregoing specific embodiments can be used to treat or preventviral infections, such as coronavirus infections (e.g., COVID-19)pursuant to the methods and uses disclosed herein.

Pharmaceutical Compositions

The present disclosure also encompasses pharmaceutical compositionscomprising siNAs of the present disclosure. One embodiment is apharmaceutical composition comprising one or more siNA of the presentdisclosure, and a pharmaceutically acceptable diluent or carrier.

In some embodiments, the pharmaceutical compositions comprising any ofthe siNA molecules, sense strands, antisense strands, first nucleotidesequences, or second nucleotide sequences described herein. Thecompositions may comprise 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12 or moresiNA molecules described herein. The compositions may comprise a firstnucleotide sequence (i.e., a sense strand) comprising a nucleotidesequence of any one SEQ ID NOs: 1-1203, 2411-3392, 4383-4604, 4827, and4828. In some embodiments, the composition comprises a second nucleotidesequence (i.e., antisense strand) comprising a nucleotide sequence ofany one of SEQ ID NOs: 1204-2406, 3393-4374, 4605-4826, 4829, and 4830.In some embodiments, the composition comprises a sense strand comprisinga nucleotide sequence of any one of SEQ ID NOs: 1-1203, 2411-3392,4383-4604, 4827, and 4828. In some embodiments, the compositioncomprises an antisense strand comprising a nucleotide sequence of anyone of SEQ ID NOs: 1204-2406, 3393-4374, 4605-4826, 4829, and 4830.

Alternatively or additionally, the pharmaceutical compositions maycomprise (a) a phosphorylation blocker; and (b) a siNA. In someembodiments, the phosphorylation blocker is any of the phosphorylationblockers disclosed herein. In some embodiments, the siNA is any of thesiNAs disclosed herein. In some embodiments, the siNA comprises any ofthe sense strands, antisense strands, first nucleotide sequences, orsecond nucleotide sequences described herein.

In some embodiments, the siNA comprises any of the sense strands,antisense strands, first nucleotide sequences, or second nucleotidesequences described herein. In some embodiments, the siNA comprises oneor more modified nucleotides. In some embodiments, the one or moremodified nucleotides are independently selected from a 2′-fluoronucleotide and a 2′-O-methyl nucleotide. In some embodiments, the2′-fluoro nucleotide or the 2′-O-methyl nucleotide is independentlyselected from any of the 2′-fluoro or 2′-O-methyl nucleotide mimicsdisclosed herein. In some embodiments, the siNA comprises a nucleotidesequence comprising any of the modification patterns disclosed herein.In some embodiments, the composition comprises (a) a conjugated moiety;and (b) a short interfering nucleic acid (siNA). In some embodiments,the siNA is any of the siNAs disclosed herein. In some embodiments, thesiNA comprises any of the sense strands, antisense strands, firstnucleotide sequences, or second nucleotide sequences described herein.

In some embodiments, the siNA comprises any of the sense strands,antisense strands, first nucleotide sequences, or second nucleotidesequences described herein. In some embodiments, the siNA comprises oneor more modified nucleotides. In some embodiments, the one or moremodified nucleotides are independently selected from a 2′-fluoronucleotide and a 2′-O-methyl nucleotide. In some embodiments, the2′-fluoro nucleotide or the 2′-O-methyl nucleotide is independentlyselected from any of the 2′-fluoro or 2′-O-methyl nucleotide mimicsdisclosed herein. In some embodiments, the siNA comprises a nucleotidesequence comprising any of the modification patterns disclosed herein.

In some embodiments, the pharmaceutical composition comprises (a) a5′-stabilized end cap; and (b) a siNA. In some embodiments, the5′-stabilized end cap is any of the 5-stabilized end caps disclosedherein. In some embodiments, the siNA is any of the siNAs disclosedherein. In some embodiments, the siNA comprises any of the sensestrands, antisense strands, first nucleotide sequences, or secondnucleotide sequences described herein. In some embodiments, the siNAcomprises one or more modified nucleotides. In some embodiments, the oneor more modified nucleotides are independently selected from a 2′-fluoronucleotide and a 2′-O-methyl nucleotide. In some embodiments, the2′-fluoro nucleotide or the 2′-O-methyl nucleotide is independentlyselected from any of the 2′-fluoro or 2′-O-methyl nucleotide mimicsdisclosed herein. In some embodiments, the siNA comprises a nucleotidesequence comprising any of the modification patterns disclosed herein.

In some embodiments, the pharmaceutical composition comprises (a) atleast one phosphorylation blocker, conjugated moiety, or 5′-stabilizedend cap; and (b) a short interfering nucleic acid (siNA). In someembodiments, the phosphorylation blocker is any of the phosphorylationblockers disclosed herein. In some embodiments, the 5′-stabilized endcap is any of the 5-stabilized end caps disclosed herein. In someembodiments, the siNA is any of the siNAs disclosed herein. In someembodiments, the siNA comprises any of the sense strands, antisensestrands, first nucleotide sequences, or second nucleotide sequencesdescribed herein. In some embodiments, the siNA comprises one or moremodified nucleotides. In some embodiments, the one or more modifiednucleotides are independently selected from a 2′-fluoro nucleotide and a2′-O-methyl nucleotide. In some embodiments, the 2′-fluoro nucleotide orthe 2′-O-methyl nucleotide is independently selected from any of the2′-fluoro or 2′-O-methyl nucleotide mimics disclosed herein. In someembodiments, the siNA comprises a nucleotide sequence comprising any ofthe modification patterns disclosed herein.

In some embodiments, the pharmaceutical composition containing the siNAof the present disclosure is formulated for systemic administration viaparenteral delivery. Parenteral administration includes intravenous,intra-arterial, subcutaneous, intraperitoneal or intramuscular injectionor infusion; also subdermal administration, e.g., via an implanteddevice. In a preferred embodiment, the pharmaceutical compositioncontaining the siNA of the present disclosure is formulated forsubcutaneous (SC) or intravenous (IV) delivery. Formulations forparenteral administration may include sterile aqueous solutions, whichmay also contain buffers, diluents and other pharmaceutically acceptableadditives as understood by the skilled artisan. For intravenous use, thetotal concentration of solutes may be controlled to render thepreparation isotonic.

The pharmaceutical compositions containing the siNA of the presentdisclosure are useful for treating a disease or disorder, e.g.,associated with the expression or activity of a coronavirus gene, morespecifically a non-structural protein, such as nsp8, nsp9, nsp10, nsp11,nsp12, nsp13, nsp14, or nsp15.

In some embodiments, the pharmaceutical composition comprises a siNA ofthe present disclosure that is complementary or hybridizes to a viraltarget RNA sequence (e.g., a non-structural protein of coronavirus), anda pharmaceutically acceptable diluent or carrier. When thepharmaceutical composition comprises two or more siNAs, the siNAs may bepresent in varying amounts. For example, in some embodiments, the weightratio of first siNA to second siNA is 1:4 to 4:1, e.g., 1:4, 1:3, 1:2,1:1, 2:1, 3:1, or 4:1. In some embodiments, the molar ratio of firstsiNA to second siNA is 1:4 to 4:1, e.g., 1:4, 1:3, 1:2, 1:1, 2:1, 3:1,or 4:1.

In some embodiments, the pharmaceutical composition comprises an amountof one or more of the siNA molecules described herein formulated withone or more pharmaceutically acceptable carriers (additives) and/ordiluents. The pharmaceutical compositions may be specially formulatedfor administration in solid or liquid form, including those adapted forthe following: (1) parenteral administration, for example, bysubcutaneous, intramuscular, intravenous or epidural injection as, forexample, a sterile solution or suspension, or sustained-releaseformulation; (2) topical application, for example, as a cream, ointment,or a controlled-release patch or spray applied to the skin; (3)intravaginally or intrarectally, for example, as a pessary, cream orfoam; (4) sublingually; (5) ocularly; (6) transdermally; or (7) nasally.

Wetting agents, emulsifiers and lubricants, such as sodium laurylsulfate and magnesium stearate, as well as coloring agents, releaseagents, coating agents, sweetening, flavoring and perfuming agents,preservatives and antioxidants can also be present in the compositions.

Examples of pharmaceutically-acceptable antioxidants include: (1) watersoluble antioxidants, such as ascorbic acid, cysteine hydrochloride,sodium bisulfate, sodium metabisulfite, sodium sulfite and the like; (2)oil-soluble antioxidants, such as ascorbyl palmitate, butylatedhydroxyanisole (BHA), butylated hydroxytoluene (BHT), lecithin, propylgallate, alpha-tocopherol, and the like; and (3) metal chelating agents,such as citric acid, ethylenediamine tetraacetic acid (EDTA), sorbitol,tartaric acid, phosphoric acid, and the like.

Formulations of the present disclosure include those suitable for nasal,topical (including buccal and sublingual), rectal, vaginal and/orparenteral administration. The formulations may conveniently bepresented in unit dosage form and may be prepared by any methods wellknown in the art of pharmacy. The amount of active ingredient which canbe combined with a carrier material to produce a single dosage form willvary depending upon the host being treated, the particular mode ofadministration. The amount of active ingredient which can be combinedwith a carrier material to produce a single dosage form will generallybe that amount of the compound (e.g., siNA molecule) which produces atherapeutic effect. Generally, out of one hundred percent, this amountwill range from about 0.1 percent to about ninety-nine percent of activeingredient, preferably from about 5 percent to about 70 percent, mostpreferably from about 10 percent to about 30 percent.

In some embodiments, a formulation of the present disclosure comprisesan excipient selected from the group consisting of cyclodextrins,celluloses, liposomes, micelle forming agents, e.g., bile acids, andpolymeric carriers, e.g., polyesters and polyanhydrides; and a compound(e.g., siNA molecule) of the present disclosure.

Methods of preparing these formulations or compositions include the stepof bringing into association a compound (e.g., siNA molecule) of thepresent disclosure with the carrier and, optionally, one or moreaccessory ingredients. In general, the formulations are prepared byuniformly and intimately bringing into association a compound (e.g.,siNA molecule) of the present disclosure with liquid carriers, or finelydivided solid carriers, or both, and then, if necessary, shaping theproduct.

Formulations of the disclosure suitable for a suspension in an aqueousor non-aqueous liquid, or as an oil-in-water or water-in-oil liquidemulsion, or as an elixir or syrup, each containing a predeterminedamount of a compound (e.g., siNA molecule) of the present disclosure asan active ingredient. A compound (e.g., siNA molecule) of the presentdisclosure may also be administered as a bolus, electuary, or paste.

In dosage forms of the disclosure, the active ingredient may be mixedwith one or more pharmaceutically-acceptable carriers, such as sodiumcitrate or dicalcium phosphate, and/or any of the following: (1) fillersor extenders, such as starches, lactose, sucrose, glucose, mannitol,and/or silicic acid; (2) binders, such as, for example,carboxymethylcellulose, alginates, gelatin, polyvinyl pyrrolidone,sucrose and/or acacia; (3) humectants, such as glycerol; (4)disintegrating agents, such as agar-agar, calcium carbonate, potato ortapioca starch, alginic acid, certain silicates, and sodium carbonate;(5) solution retarding agents, such as paraffin; (6) absorptionaccelerators, such as quaternary ammonium compounds and surfactants,such as poloxamer and sodium lauryl sulfate; (7) wetting agents, suchas, for example, cetyl alcohol, glycerol monostearate, and non-ionicsurfactants; (8) absorbents, such as kaolin and bentonite clay; (9)lubricants, such as talc, calcium stearate, magnesium stearate, solidpolyethylene glycols, sodium lauryl sulfate, zinc stearate, sodiumstearate, stearic acid, and mixtures thereof; (10) coloring agents; and(11) controlled release agents such as crospovidone or ethyl cellulose.

The disclosed dosage forms may be sterilized by, for example, filtrationthrough a bacteria-retaining filter, or by incorporating sterilizingagents in the form of sterile solid compositions which can be dissolvedin sterile water, or some other sterile injectable medium immediatelybefore use. These compositions may also optionally contain opacifyingagents and may be of a composition that they release the activeingredient(s) only, or preferentially, in a certain portion of thegastrointestinal tract, optionally, in a delayed manner. Examples ofembedding compositions which can be used include polymeric substancesand waxes. The active ingredient can also be in micro-encapsulated form,if appropriate, with one or more of the above-described excipients.

Liquid dosage forms of the compounds (e.g., siNA molecules) of thedisclosure include pharmaceutically acceptable emulsions,microemulsions, solutions, suspensions, syrups and elixirs. In additionto the active ingredient, the liquid dosage forms may contain inertdiluents commonly used in the art, such as, for example, water or othersolvents, solubilizing agents and emulsifiers, such as ethyl alcohol,isopropyl alcohol, ethyl carbonate, ethyl acetate, benzyl alcohol,benzyl benzoate, propylene glycol, 1,3-butylene glycol, oils (Iparticular, cottonseed, groundnut, corn, germ, olive, castor and sesameoils), glycerol, tetrahydrofuryl alcohol, polyethylene glycols and fattyacid esters of sorbitan, and mixtures thereof.

Besides inert diluents, the compositions can also include adjuvants suchas wetting agents, emulsifying and suspending agents, sweetening,flavoring, coloring, perfuming and preservative agents.

Suspensions, in addition to the active compounds (e.g., siNA molecules),may contain suspending agents as, for example, ethoxylated isostearylalcohols, polyoxyethylene sorbitol and sorbitan esters, microcrystallinecellulose, aluminum metahydroxide, bentonite, agar-agar and tragacanth,and mixtures thereof.

Formulations of the pharmaceutical compositions of the disclosure forrectal or vaginal administration may be presented as a suppository,which may be prepared by mixing one or more compounds (e.g., siNAmolecules) of the disclosure with one or more suitable nonirritatingexcipients or carriers comprising, for example, cocoa butter,polyethylene glycol, a suppository wax or a salicylate, and which issolid at room temperature, but liquid at body temperature and,therefore, will melt in the rectum or vaginal cavity and release theactive compound (e.g., siNA molecule).

Formulations of the present disclosure which are suitable for vaginaladministration also include pessaries, tampons, creams, gels, pastes,foams or spray formulations containing such carriers as are known in theart to be appropriate.

Dosage forms for the topical or transdermal administration of a compound(e.g., siNA molecule) of this disclosure include powders, sprays,ointments, pastes, creams, lotions, gels, solutions, patches andinhalants. The active compound (e.g., siNA molecule) may be mixed understerile conditions with a pharmaceutically acceptable carrier, and withany preservatives, buffers, or propellants which may be required.

The ointments, pastes, creams and gels may contain, in addition to anactive compound (e.g., siNA molecule) of this disclosure, excipients,such as animal and vegetable fats, oils, waxes, paraffins, starch,tragacanth, cellulose derivatives, polyethylene glycols, silicones,bentonites, silicic acid, talc and zinc oxide, or mixtures thereof.

Powders and sprays can contain, in addition to a compound (e.g., siNAmolecule) of this disclosure, excipients such as lactose, talc, silicicacid, aluminum hydroxide, calcium silicates and polyamide powder, ormixtures of these substances. Sprays can additionally contain customarypropellants, such as chlorofluorohydrocarbons and volatile unsubstitutedhydrocarbons, such as butane and propane.

Transdermal patches have the added advantage of providing controlleddelivery of a compound (e.g., siNA molecule) of the present disclosureto the body. Such dosage forms can be made by dissolving or dispersingthe compound (e.g., siNA molecule) in the proper medium. Absorptionenhancers can also be used to increase the flux of the compound (e.g.,siNA molecule) across the skin. The rate of such flux can be controlledby either providing a rate controlling membrane or dispersing thecompound (e.g., siNA molecule) in a polymer matrix or gel.

Ophthalmic formulations, eye ointments, powders, solutions and the like,are also contemplated as being within the scope of this invention.

Pharmaceutical compositions of this disclosure suitable for parenteraladministration comprise one or more compounds (e.g., siNA molecules) ofthe disclosure in combination with one or morepharmaceutically-acceptable sterile isotonic aqueous or nonaqueoussolutions, dispersions, suspensions or emulsions, or sterile powderswhich may be reconstituted into sterile injectable solutions ordispersions just prior to use, which may contain sugars, alcohols,antioxidants, buffers, bacteriostats, solutes which render theformulation isotonic with the blood of the intended recipient orsuspending or thickening agents.

Examples of suitable aqueous and nonaqueous carriers which may beemployed in the pharmaceutical compositions of the disclosure includewater, ethanol, polyols (such as glycerol, propylene glycol,polyethylene glycol, and the like), and suitable mixtures thereof,vegetable oils, such as olive oil, and injectable organic esters, suchas ethyl oleate. Proper fluidity can be maintained, for example, by theuse of coating materials, such as lecithin, by the maintenance of therequired particle size in the case of dispersions, and by the use ofsurfactants.

These compositions may also contain adjuvants such as preservatives,wetting agents, emulsifying agents and dispersing agents. Prevention ofthe action of microorganisms upon the subject compounds may be ensuredby the inclusion of various antibacterial and antifungal agents, forexample, paraben, chlorobutanol, phenol sorbic acid, and the like. Itmay also be desirable to include isotonic agents, such as sugars, sodiumchloride, and the like into the compositions. In addition, prolongedabsorption of the injectable pharmaceutical form may be brought about bythe inclusion of agents which delay absorption such as aluminummonostearate and gelatin.

In some cases, in order to prolong the effect of a drug, it is desirableto slow the absorption of the drug from subcutaneous or intramuscularinjection. This may be accomplished by the use of a liquid suspension ofcrystalline or amorphous material having poor water solubility. The rateof absorption of the drug then depends upon its rate of dissolutionwhich, in turn, may depend upon crystal size and crystalline form.Alternatively, delayed absorption of a parenterally-administered drugform is accomplished by dissolving or suspending the drug in an oilvehicle.

Injectable depot forms are made by forming microencapsule matrices ofthe subject compounds (e.g., siNA molecules) in biodegradable polymerssuch as polylactide-polyglycolide. Depending on the ratio of drug topolymer, and the nature of the particular polymer employed, the rate ofdrug release can be controlled. Examples of other biodegradable polymersinclude poly(orthoesters) and poly(anhydrides). Depot injectableformulations are also prepared by entrapping the drug in liposomes ormicroemulsions which are compatible with body tissue.

When the compounds (e.g., siNA molecules) of the present disclosure areadministered as pharmaceuticals, to humans and animals, they can begiven per se or as a pharmaceutical composition containing, for example,0.1 to 99% (more preferably, 10 to 30%) of active ingredient incombination with a pharmaceutically acceptable carrier.

Methods of Treatment and Administration

The siNA molecules of the present disclosure may be used to treat orprevent a disease in a subject in need thereof. In some embodiments, amethod of treating or preventing a disease in a subject in need thereofcomprises administering to the subject any of the siNA moleculesdisclosed herein. In some embodiments, a method of treating orpreventing a disease in a subject in need thereof comprisesadministering to the subject any of the compositions disclosed herein.

In some embodiments of the disclosed methods and uses, the disease is arespiratory disease. In some embodiments, the respiratory disease is aviral infection. In some embodiments, the respiratory disease is viralpneumonia. In some embodiments, the respiratory disease is an acuterespiratory infection. In some embodiments, the respiratory disease is acold. In some embodiments, the respiratory disease is severe acuterespiratory syndrome (SARS). In some embodiments, the respiratorydisease is Middle East respiratory syndrome (MERS). In some embodiments,the disease is coronavirus disease 2019 (e.g., COVID-19). In someembodiments, the respiratory disease can include one or more symptomsselected from coughing, sore throat, runny nose, sneezing, headache,fever, shortness of breath, myalgia, abdominal pain, fatigue, difficultybreathing, persistent chest pain or pressure, difficulty waking, loss ofsmell and taste, muscle or joint pain, chills, nausea or vomiting, nasalcongestion, diarrhea, haemoptysis, conjunctival congestion, sputumproduction, chest tightness, and palpitations. In some embodiments, therespiratory disease can include complications selected from sinusitis,otitis media, pneumonia, acute respiratory distress syndrome,disseminated intravascular coagulation, pericarditis, and kidneyfailure. In some embodiments, the respiratory disease is idiopathic.

In some embodiments, the subject is a mammal. In some embodiments, thesubject is a human. In some embodiments, the subject is a non-humanprimate. In some embodiments, the subject is a cat. In some embodiments,the subject is a camel. In preferred embodiments in which the subject isa human, the subject may be at least 40 years old, at least 45 yearsold, at least 50 years old, at least 55 years old, at least 60 yearsold, at least 65 years old, at least 70 years old, at least 75 yearsold, or at least 80 years old or older. In some embodiments, the subjectis a pediatric subject (i.e., less than 18 years old).

The preparations (e.g., siNA molecules or pharmaceutical compositionsthereof) of the present disclosure may be given parenterally, topically,or rectally or administered in the form of an inhalant. They are, ofcourse, given in forms suitable for each administration route. Forexample, they are administered in tablets or capsule form,administration by injection, infusion, or inhalation; topical by lotionor ointment; rectal by suppositories. Injection, infusion, or inhalationare preferred.

These compounds may be administered to humans and other animals fortherapy or as a prophylactic by any suitable route of administration,including nasally (as by, for example, a spray), rectally,intravaginally, parenterally, intracisternally and topically, as bypowders, ointments or drops, including buccally and sublingually. Insome embodiments, the compounds or compositions are inhaled, as by, forexample, an inhaler, a nebulizer, or in an aerosolized form.

Regardless of the route of administration selected, the compounds (e.g.,siNA molecules) of the present disclosure, which may be used in asuitable hydrated form, and/or the pharmaceutical compositions of thepresent disclosure, are formulated into pharmaceutically-acceptabledosage forms by conventional methods known to those of skill in the art.

In some embodiments, the present disclosure provides methods of treatingor preventing a coronavirus infection, comprising administering to asubject in need thereof a therapeutically effective amount of one ormore of the siNAs or a pharmaceutical composition as disclosed herein.In some embodiments, the coronavirus infection is selected from thegroup consisting of Middle East Respiratory Syndrome (MERS), SevereAcute Respiratory Syndrome (SARS), and COVID-19. In some embodiments,the subject has been treated with one or more additional coronavirustreatment agents. In some embodiments, the subject is concurrentlytreated with one or more additional coronavirus treatment agents.

Actual dosage levels of the active ingredients (e.g., siNA molecules) inthe pharmaceutical compositions of this disclosure may be varied so asto obtain an amount of the active ingredient which is effective toachieve the desired therapeutic response for a particular patient,composition, and mode of administration, without being toxic to thepatient.

The selected dosage level will depend upon a variety of factorsincluding the activity of the particular compound (e.g., siNA molecule)of the present disclosure employed, or the ester, salt or amide thereof,the route of administration, the time of administration, the rate ofexcretion or metabolism of the particular compound being employed, therate and extent of absorption, the duration of the treatment, otherdrugs, compounds and/or materials used in combination with theparticular compound employed, the age, sex, weight, condition, generalhealth and prior medical history of the patient being treated, and likefactors well known in the medical arts.

A physician or veterinarian having ordinary skill in the art can readilydetermine and prescribe the effective amount of the pharmaceuticalcomposition required. For example, the physician or veterinarian couldstart doses of the compounds (e.g., siNA molecules) of the disclosureemployed in the pharmaceutical composition at levels lower than thatrequired in order to achieve the desired therapeutic effect andgradually increase the dosage until the desired effect is achieved.

In general, a suitable daily dose of a compound (e.g., siNA molecule) ofthe disclosure is the amount of the compound that is the lowest doseeffective to produce a therapeutic effect. Such an effective dosegenerally depends upon the factors described above. Preferably, thecompounds are administered at about 0.01 mg/kg to about 200 mg/kg, morepreferably at about 0.1 mg/kg to about 100 mg/kg, even more preferablyat about 0.5 mg/kg to about 50 mg/kg. In some embodiments, the compoundis administered at a dose equal to or greater than 0.01, 0.02, 0.03,0.04, 0.05, 0.06, 0.07, 0.08, 0.09, 0.10, 0.11, 0.12, 0.13, 0.14, 0.15,0.16, 0.17, 0.18, 0.19, 0.20, 0.21, 0.22, 0.23, 0.24, 0.25, 0.26, 0.27,0.28, 0.29, 0.30, 0.35, 0.40, 0.45, 0.50, 0.55, 0.60, 0.65, 0.7, 0.75,0.8, 0.85, 0.9, 0.95, or 1 mg/kg. In some embodiments, the compound isadministered at a dose equal to or less than 200, 190, 180, 170, 160,150, 140, 130, 120, 110, 100, 95, 90, 85, 80, 75, 70, 65, 60, 55, 50,45, 40, 35, 30, 25, 20, or 15 mg/kg. In some embodiments, the totaldaily dose of the compound is equal to or greater than 10, 15, 20, 25,30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80, 85, 90, 95, 100, 105, 110,115, 120, 125, 130, 135, 140, 145, 150, 155, 160, 165, 170, 175, 180,185, 190, 195, or 100 mg.

If desired, the effective daily dose of the active compound (e.g., siNA)may be administered as two, three, four, five, six, seven, eight, nine,ten or more doses or sub-doses administered separately at appropriateintervals throughout the day, optionally, in unit dosage forms. In someembodiments, the compound is administered at least 1, 2, 3, 4, 5, 6, 7,8, 9, 10, 11, 12, 13, 14, or 15 times. Preferred dosing is oneadministration per day. In some embodiments, the compound isadministered at least 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15,16, 17, 18, 19, 20, or 21 times a week. In some embodiments, thecompound is administered at least 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12,13, 14, 15, 16, 17, 18, 19, 20, or 21 times a month. In someembodiments, the compound is administered once every 1, 2, 3, 4, 5, 6,7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, or 21 days. In someembodiments, the compound is administered every 3 days. In someembodiments, the compound is administered once every 1, 2, 3, 4, 5, 6,7, 8, 9, 10, 11, 12, 13, 14, or 15 weeks. In some embodiments, thecompound is administered every month. In some embodiments, the compoundis administered once every 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13,14, or 15 months. In some embodiments, the compound is administered atleast 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19,20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37,38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, or 53 timesover a period of at least 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14,15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32,33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50,51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68,69, or 70 days. In some embodiments, the compound is administered atleast 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19,20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37,38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, or 53 timesover a period of at least 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14,15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32,33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50,51, 52, or 53 weeks. In some embodiments, the compound is administeredat least 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18,19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36,37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, or 53times over a period of at least 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12,13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30,31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48,49, 50, 51, 52, or 53 months. In some embodiments, the compound isadministered at least once a week for a period of at least 1, 2, 3, 4,5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23,24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41,42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59,60, 61, 62, 63, 64, 65, 66, 67, 68, 69, or 70 weeks. In someembodiments, the compound is administered at least once a week for aperiod of at least 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15,16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33,34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51,52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69,or 70 months. In some embodiments, the compound is administered at leasttwice a week fora period of at least 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11,12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29,30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47,48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65,66, 67, 68, 69, or 70 weeks. In some embodiments, the compound isadministered at least twice a week for a period of at least 1, 2, 3, 4,5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23,24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41,42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59,60, 61, 62, 63, 64, 65, 66, 67, 68, 69, or 70 months. In someembodiments, the compound is administered at least once every two weeksfor a period of at least 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15,16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33,34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51,52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69,or 70 weeks. In some embodiments, the compound is administered at leastonce every two weeks for a period of at least 2, 3, 4, 5, 6, 7, 8, 9,10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27,28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45,46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63,64, 65, 66, 67, 68, 69, or 70 months. In some embodiments, the compoundis administered at least once every four weeks fora period of at least4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22,23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40,41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58,59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, or 70 weeks. In someembodiments, the compound is administered at least once every four weeksfor a period of at least 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16,17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34,35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52,53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, or70 months.

In some embodiments, any one of the siNAs or compositions disclosedherein is administered in a particle or viral vector. In someembodiments, the viral vector is a vector of adenovirus,adeno-associated virus (AAV), alphavirus, flavivirus, herpes simplexvirus, lentivirus, measles virus, picornavirus, poxvirus, retrovirus, orrhabdovirus. In some embodiments, the viral vector is a recombinantviral vector. In some embodiments, the viral vector is selected fromAAVrh.74, AAVrh.10, AAVrh.20, AAV-1, AAV-2, AAV-3, AAV-4, AAV-5, AAV-6,AAV-7, AAV-8, AAV-9, AAV-10, AAV-11, AAV-12 and AAV-13.

The subject of the described methods may be a mammal, and it includeshumans and non-human mammals. In some embodiments, the subject is ahuman, such as an adult human.

The disclosed siNA can be administered alone or in combination with oneor more additional coronavirus treatment agents and/or antiviral agents.The additional coronavirus treatment agent and/or antiviral may be asmall molecule (e.g., a nucleoside analog or a protease inhibitor) or abiologic (e.g., an antibody or peptide). Examples of suitablecoronavirus treatment agents include, but are not limited to,remdesivir, favipiravir, molnupiravir, dexamethasone, bamlanivimab,casirivimab, imdevimab, convalescent plasma, and interferons. Examplesof suitable antiviral agents include, but are not limited to, baloxavirmarboxil, oseltamivir, anamivir, vidarabine, acyclovir, ganciclovir,zidovudine, didanosine, zalcitabine, lamivudine, saquinavir, ritonavir,indinavir, nelfinavir, ribavirin, amantadine, rimantadine, remdesivir,favipiravir, and molnupiravir.

When the compounds (e.g., siNA molecules) described herein areco-administered with another, the effective amount may be less than whenthe compound is used alone.

Examples Example 1: siNA Synthesis

This example describes an exemplary method for synthesizing ds-siNAs,such as the siNAs disclosed in Table 6 (as identified by the ds-siNAID).

The 2′-OMe phosphoramidite 5′-O-DMT-deoxy Adenosine (NH-Bz),3′-O-(2-cyanoethyl-N,N-diisopropyl phosphoramidite, 5′-O-DMT-deoxyGuanosine (NH-ibu), 3′-O-(2-cyanoethyl-N,N-diisopropyl phosphoramidite,5′-O-DMT-deoxy Cytosine (NH-Bz), 3′-O-(2-cyanoethyl-N,N-diisopropylphosphoramidite, 5′-O-DMT-Uridine 3′-O-(2-cyanoethyl-N,N-diisopropylphosphoramidite and solid supports were purchased from Chemgenes Corp.MA.

The 2′-F-5′-O-DMT-(NH-Bz) Adenosine-3′-O-(2-cyanoethyl-N,N-diisopropylphosphoramidite, 2′-F-5′-O-DMT-(NH-ibu)-Guanosine,3′-O-(2-cyanoethyl-N,N-diisopropyl phosphoramidite,5′-O-DMT-(NH-Bz)-Cytosine, 2′-F-3′-O-(2-cyanoethyl-N,N-diisopropylphosphoramidite, 5′-O-DMT-Uridine,2′-F-3′-O-(2-cyanoethyl-N,N-diisopropyl phosphoramidite and solidsupports were purchased from Thermo Fischer Milwaukee Wis., USA.

All the monomers were dried in vacuum desiccator with desiccants (P₂O₅,RT 24 h). The solid supports (CPG) attached to the nucleosides anduniversal supports was obtained from LGC and Chemgenes. The chemicalsand solvents for post synthesis workflow were purchased fromcommercially available sources like VWR/Sigma and used without anypurification or treatment. Solvent (Acetonitrile) and solutions (amiditeand activator) were stored over molecular sieves during synthesis.

The oligonucleotides were synthesized on a DNA/RNA Synthesizers(Expedite 8909 or ABI-394) using standard oligonucleotidephosphoramidite chemistry starting from the 3′ residue of theoligonucleotide preloaded on CPG support. An extended coupling of 0.1Msolution of phosphoramidite in CH₃CN in the presence of5-(ethylthio)-1H-tetrazole activator to a solid bound oligonucleotidefollowed by standard capping, oxidation and deprotection affordedmodified oligonucleotides. The 0.1M 12, THF:Pyridine; Water-7:2:1 wasused as oxidizing agent while DDTT ((dimethylamino-methylidene)amino)-3H-1,2,4-dithiazaoline-3-thione was used as the sulfur-transferagent for the synthesis of oligoribonucleotide phosphorothioates. Thestepwise coupling efficiency of all modified phosphoramidites was morethan 98%.

Reagents Detailed Description Deblock Solution 3% Dichloroacetic acid(DCA) in Dichloromethane (DCM) Amidite Concentration 0.1M in AnhydrousAcetonitrile Activator 0.25M Ethyl-thio-Tetrazole (ETT) Cap-A solutionAcetic anhydride in Pyridine/THF Cap-B Solution 16% 1-Methylimidazole inTHF Oxidizing Solution 0.02M I₂, THF:Pyridine; Water-7:2:1 SulfurizingSolution 0.2M DDTT in Pyridine/Acetonitrile 1:1

Cleavage and Deprotection

Deprotection and cleavage from the solid support was achieved withmixture of ammonia methylamine (1:1, AMA) for 15 min at 65° C., when theuniversal linker was used, the deprotection was left for 90 min at 65°C. or solid supports were heated with aqueous ammonia (28%) solution at55° C. for 16 h to deprotect the base labile protecting groups.

Quantitation of Crude SiNA or Raw Analysis

Samples were dissolved in deionized water (1.0 mL) and quantitated asfollows: Blanking was first performed with water alone (2 ul) onNanodrop then Oligo sample reading obtained at 260 nm. The crudematerial is dried down and stored at −20° C.

Crude HPLC/LC-MS analysis

The 0.1 OD of the crude samples were analyzed for crude HPLC and LC-MSanalysis. After Confirming the crude LC-MS data then purification stepwas performed.

HPLC Purification

The unconjugated oligonucleotides were purified by anion-exchange HPLC.The buffers were 20 mM sodium phosphate in 10% CH₃CN, pH 8.5 (buffer A)and 20 mM sodium phosphate in 10% CH₃CN, 1.0 M NaBr, pH 8.5 (buffer B).Fractions containing full-length oligonucleotides were pooled.

Desalting of Purified SiNA

The purified dry siNA was then desalted using Sephadex G-25 M (AmershamBiosciences). The cartridge was conditioned with 10 mL of deionizedwater thrice. Finally, the purified siNA dissolved thoroughly in 2.5 mLRNAse free water was applied to the cartridge with very slow drop wiseelution. The salt free siNA was eluted with 3.5 ml deionized waterdirectly into a screw cap vial.

IEX HPLC and Electrospray LC/MS Analysis

Approximately 0.10 OD of siNA is dissolved in water and then pipetted inspecial vials for IEX-HPLC and LC/MS analysis. Analytical HPLC and ESLC-MS established the integrity of the compounds.

Duplex Preparation

Single strand oligonucleotides (Sense and Antisense strands) wereannealed (1:1 by molar equivalents, heat 90° C. for 3 min followed byroom temperature, 20 min) to give the duplex ds-siNA. The finalcompounds were analyzed on size exclusion chromatography (SEC).

Example 2: Synthesis of 5′ End Cap Monomer

Example 2 Monomer Synthesis Scheme

Preparation of (2): To a solution of 1 (15 g, 57.90 mmol) in DMF (150mL) were added AcSK (11.24 g, 98.43 mmol) and TBAI (1.07 g, 2.89 mmol),and the mixture was stirred at 25° C. for 12 h. Upon completion asmonitored by LCMS, the mixture was diluted with H₂O (10 mL) andextracted with EA (200 mL*3). The combined organic layers were washedwith brine (200 mL*3), dried over anhydrous Na₂SO₄, filtered andconcentrated under reduced pressure to give 2 (14.5 g, 96.52% yield, 98%purity) as a colorless oil. ESI-LCMS: 254.28 [M+H]⁺; ¹H NMR (400 MHz,CDCl₃) δ=4.78-4.65 (m, 2H), 3.19 (d, J=14.1 Hz, 2H), 2.38 (s, 3H), 1.32(t, J=6.7 Hz, 12H); ³¹P NMR (162 MHz, CDCl₃) δ=20.59.

Preparation of (3): To a solution of 2 (14.5 g, 57.02 mmol) in CH₃CN (50mL) and MeOH (25 mL) was added NaOH (3 M, 28.51 mL), and the mixture wasstirred at 25° C. for 12 h under Ar. Upon completion as monitored byTLC, the reaction mixture was concentrated under reduced pressure toremove CH₃CN and CH₃OH. The residue was diluted with water (50 mL) andadjust pH=7 by 6M HCl, and the mixture was extracted with EA (50 mL*3).The combined organic layers were washed with brine (50 mL*3), dried overanhydrous Na₂SO₄, filtered and concentrated under reduced pressure togive 3 (12.1 g, crude) as a colorless oil.

Preparation of (4): To a solution of 3 (12.1 g, 57.01 mmol) in CH₃CN (25mL) and MeOH (25 mL) was added A (14.77 g, 57.01 mmol) dropwise at 25°C., and the mixture was stirred at 25° C. under Ar for 12 h. Uponcompletion as monitored by LCMS, the reaction mixture was concentratedunder reduced pressure to give 4 (19.5 g, 78.85% yield) as a colorlessoil. ¹H NMR (400 MHz, CDCl₃) δ=4.80-4.66 (m, 4H), 2.93 (d, J=11.3 Hz,4H), 1.31 (dd, J=3.9, 6.1 Hz, 24H); ³¹P NMR (162 MHz, CDCl₃) δ=22.18.

Preparation of (5): To a solution of 4 (19.5 g, 49.95 mmol) in MeOH (100mL) and H₂O (100 mL) was added Oxone (61.41 g, 99.89 mmol) at 25° C. inportions, and the mixture was stirred at 25° C. for 12 h under Ar. Uponcompletion as monitored by LCMS, the reaction mixture was filtered, andthe filtrate was concentrated under reduced pressure to remove MeOH. Theresidue was extracted with EA (50 mL*3). The combined organic layerswere washed with brine (50 mL*3), dried over anhydrous Na₂SO₄, filteredand concentrated under reduced pressure to give a residue. The crudeproduct was triturated with i-Pr₂O and n-Hexane (1:2, 100 mL) at 25° C.for 30 min to give 5 (15.6 g, 73.94% yield,) as a white solid. ¹H NMR(400 MHz, CDCl₃) δ=4.92-4.76 (m, 4H), 4.09 (d, J=16.1 Hz, 4H), 1.37 (dd,J=3.5, 6.3 Hz, 24H); ³¹P NMR (162 MHz, CDCl₃) δ=10.17.

Preparation of (7): To a mixture of 5 (6.84 g, 16.20 mmol) in THF (20mL) was added LiBr (937.67 mg, 10.80 mmol) until dissolved, followed byDIEA (1.40 g, 10.80 mmol, 1.88 mL) under argon at 15° C. The mixture wasstirred at 15° C. for 15 min. 6 (4 g, 10.80 mmol) were added. Themixture was stirred at 15° C. for 3 h. Upon completion as monitored byLCMS, the reaction mixture was quenched by addition of H₂O (40 mL) andextracted with EA (40 mL*3). The combined organic layers were washedwith brine (100 mL), dried over Na₂SO₄, filtered and concentrated underreduced pressure to give a residue. The residue was purified by flashreverse-phase chromatography (120 g C-18 Column, Eluent of 0˜60% ACN/H₂Ogradient @ 80 mL/min) to give 7 (5.7 g, 61.95% yield) as a colorlessoil. ESI-LCMS: 611.2 [M+H]⁺, ¹H NMR (400 MHz, CDCl₃); δ=9.26 (s, 1H),7.50 (d, J=8.1 Hz, 1H), 7.01 (s, 2H), 5.95 (d, J=2.7 Hz, 1H), 5.80 (dd,J=2.1, 8.2 Hz, 1H), 4.89-4.72 (m, 2H), 4.66 (d, J=7.2 Hz, 1H), 4.09-4.04(m, 1H), 3.77 (dd, J=2.7, 4.9 Hz, 1H), 3.62 (d, J=3.1 Hz, 1H), 3.58 (d,J=3.1 Hz, 1H), 3.52 (s, 3H), 1.36 (td, J=1.7, 6.1 Hz, 12H), 0.92 (s,9H), 0.12 (s, 6H); ³¹P NMR (162 MHz, CDCl₃) δ=9.02

Preparation of (8): To a mixture of 7 (5.4 g, 8.84 mmol) in THF (80 mL)was added Pd/C (5.4 g, 10% purity) under N₂. The suspension was degassedunder vacuum and purged with H₂ several times. The mixture was stirredunder H₂ (15 psi) at 20° C. for 1 hr. Upon completion as monitored byLCMS, the reaction mixture was filtered, and the filtrate wasconcentrated to give 8 (5.12 g, 94.5% yield) as a white solid. ESI-LCMS:613.3 [M+H]⁺; H NMR (400 MHz, CD₃CN) δ=9.31 (s, 1H), 7.37 (d, J=8.0 Hz,1H), 5.80-5.69 (m, 2H), 4.87-4.75 (m, 2H), 4.11-4.00 (m, 1H), 3.93-3.85(m, 1H), 3.80-3.74 (m, 1H), 3.66-3.60 (m, 1H), 3.57-3.52 (m, 1H), 3.49(s, 3H), 3.46-3.38 (m, 1H), 2.35-2.24 (m, 1H), 2.16-2.03 (m, 1H),1.89-1.80 (m, 1H), 1.37-1.34 (m, 12H), 0.90 (s, 9H), 0.09 (s, 6H); ³¹PNMR (162 MHz, CD₃CN) δ=9.41.

Preparation of (9): To a solution of 8 (4.4 g, 7.18 mmol) in THF (7.2mL) was added TBAF (1 M, 7.18 mL), and the mixture was stirred at 20° C.for 1 hr. Upon completion as monitored by LCMS, the reaction mixture wasdiluted with H₂O (50 mL) and extracted with EA (50 mL*4). The combinedorganic layers were washed with brine (50 mL), dried over Na₂SO₄,filtered and concentrated under reduced pressure to give a residue. Theresidue was purified by flash silica gel chromatography (ISCO®; 40 gSepaFlash® Silica Flash Column, Eluent of 0˜5%, MeOH/DCM gradient @ 40mL/min) to give 9 (3.2 g, 88.50% yield) as a white solid. ESI-LCMS:499.2 [M+H]⁺¹; ¹H NMR (400 MHz, CD₃CN) δ=9.21 (s, 1H), 7.36 (d, J=8.3Hz, 1H), 5.81-5.72 (m, 2H), 4.88-4.74 (m, 2H), 3.99-3.87 (m, 2H), 3.84(dd, 5.4 Hz, 1H), 3.66-3.47 (m, 7H), 2.98 (s, 1H), 2.44-2.15 (m, 2H),1.36 (d, J=6.0 Hz, 12H); ³¹P NMR (162 MHz, CD₃CN) δ=9.48.

Preparation of (Example 2 monomer): To a mixture of 9 (3.4 g, 6.82 mmol,1 eq) and 4 A MS (3.4 g) in MeCN (50 mL) was added P1 (2.67 g, 8.87mmol, 2.82 mL, 1.3 eq) at 0° C., followed by addition of1H-imidazole-4,5-dicarbonitrile (886.05 mg, 7.50 mmol) at 0° C. Themixture was stirred at 20° C. for 2 h. Upon completion as monitored byLCMS, the reaction mixture was quenched by addition of saturated aq.NaHCO₃ (50 mL) and diluted with DCM (100 mL). The organic layer waswashed with saturated aq. NaHCO₃ (50 mL*2), dried over Na₂SO₄, filteredand concentrated under reduced pressure to give a residue. The residuewas purified by prep-HPLC: column: YMC-Triart Prep C18 250*50 mm*10 um;mobile phase: [water (10 mM NH₄HCO₃)-ACN]; B %: 15% to give a impureproduct. The impure product was further purified by a flash silica gelcolumn (0% to 5% i-PrOH in DCM with 0.5% TEA) to give Example 2 monomer(2.1 g, 43.18% yield) as a white solid. ESI-LCMS: 721.2 [M+Na]⁺; H NMR(400 MHz, CD₃CN) δ=9.29 (s, 1H), 7.45 (d, J=8.1 Hz, 1H), 5.81 (d, J=4.2Hz, 1H), 5.65 (d, J=8.1 Hz, 1H), 4.79-4.67 (m, 2H), 4.26-4.05 (m, 2H),4.00-3.94 (m, 1H), 3.89-3.63 (m, 6H), 3.53-3.33 (m, 5H), 2.77-2.61 (m,2H), 2.31-2.21 (m, 1H), 2.16-2.07 (m, 1H), 1.33-1.28 (m, 12H), 1.22-1.16(m, 1H), 1.22-1.16 (m, 11H); ³¹P NMR (162 MHz, CD₃CN) δ=149.89, 149.78,10.07, 10.02.

Example 3: Synthesis of 5′ End Cap Monomer

Example 3 Monomer Synthesis Scheme

Preparation of (2): To a solution of 1 (5 g, 13.42 mmol) in DMF (50 mL)were added PPh₃ (4.58 g, 17.45 mmol) and 2-hydroxyisoindoline-1,3-dione(2.85 g, 17.45 mmol), followed by a solution of DIAD (4.07 g, 20.13mmol, 3.91 mL) in DMF (10 mL) dropwise at 15° C. The resulting solutionwas stirred at 15° C. for 18 hr. The reaction mixture was then dilutedwith DCM (50 mL), washed with H₂O (60 mL*3) and brine (30 mL), driedover Na₂SO₄, filtered and evaporated to give a residue. The residue wasthen triturated with EtOH (55 mL) for 30 min, and the collected whitepowder was washed with EtOH (10 mL*2) and dried to give 2 (12.2 g,85.16% yield) as a white powder (the reaction was set up in two batchesand combined) ESI-LCMS: 518.1 [M+H]⁺.

Preparation of (3): 2 (6 g, 11.59 mmol) was suspended in MeOH (50 mL),and then NH₂NH₂.H₂O (3.48 g, 34.74 mmol, 3.38 mL, 50% purity) was addeddropwise at 20° C. The reaction mixture was stirred at 20° C. for 4 hr.Upon completion, the reaction mixture was diluted with EA (20 mL) andwashed with NaHCO₃ (10 mL*2) and brine (10 mL). The combined organiclayers were then dried over Na₂SO₄, filtered and evaporated to give 3(8.3 g, 92.5% yield) as a white powder. (The reaction was set up in twobatches and combined). ESI-LCMS: 388.0 [M+H]⁺, ¹H NMR (400 MHz, DMSO-d₆)δ=11.39 (br s, 1H), 7.72 (d, J=8.1 Hz, 1H), 6.24-6.09 (m, 2H), 5.80 (d,J=4.9 Hz, 1H), 5.67 (d, J=8.1 Hz, 1H), 4.26 (t, J=4.9 Hz, 1H), 4.03-3.89(m, 1H), 3.87-3.66 (m, 3H), 3.33 (s, 3H), 0.88 (s, 9H), 0.09 (d, J=1.3Hz, 6H)

Preparation of (4): To a solution of 3 (7 g, 18.06 mmol) and Py (1.43 g,18.06 mmol, 1.46 mL) in DCM (130 mL) was added a solution of MSCl (2.48g, 21.68 mmol, 1.68 mL) in DCM (50 mL) dropwise at −78° C. under N₂. Thereaction mixture was allowed to warm to 15° C. in 30 min and stirred at15° C. for 3 h. The reaction mixture was quenched by addition ofice-water (70 mL) at 0° C., and then extracted with DCM (50 mL*3). Thecombined organic layers were washed with saturated aq. NaHCO₃ (50 mL)and brine (30 mL), dried over Na₂SO₄, filtered and concentrated underreduced pressure to give a residue. The residue was purified by flashsilica gel chromatography (ISCO®; 30 g SepaFlash® Silica Flash Column,Eluent of 0˜20% i-PrOH/DCM gradient @ 30 mL/min to give 4 (6.9 g, 77.94%yield) as a white solid. ESI-LCMS: 466.1 [M+H]⁺, ¹H NMR (400 MHz,DMSO-d₆) δ=11.41 (br s, 1H), 10.15 (s, 1H), 7.69 (d, J=8.1 Hz, 1H), 5.80(d, J=4.4 Hz, 1H), 5.65 (d, J=8.1 Hz, 1H), 4.24 (t, J=5.2 Hz, 1H),4.16-3.98 (m, 3H), 3.87 (t, J=4.8 Hz, 1H), 3.00 (s, 3H), 2.07 (s, 3H),0.88 (s, 9H), 0.10 (d, J=1.5 Hz, 6H)

Preparation of (5): To a solution of 4 (6.9 g, 14.82 mmol) in THF (70mL) was added TBAF (1 M, 16.30 mL) at 15° C. The reaction mixture wasstirred at 15° C. for 18 hr, and then evaporated to give a residue. Theresidue was purified by flash silica gel chromatography (ISCO®; 24 gSepaFlash® Silica Flash Column, Eluent of 0˜9% MeOH/Ethyl acetategradient @ 30 mL/min) to give 5 (1.8 g, 50.8% yield) as a white solid.ESI-LCMS: 352.0 [M+H]⁺; ¹H NMR (400 MHz, DMSO-d₆) δ=11.40 (s, 1H), 10.13(s, 1H), 7.66 (d, J=8.1 Hz, 1H), 5.83 (d, J=4.9 Hz, 1H), 5.65 (dd,J=1.8, 8.1 Hz, 1H), 5.36 (d, J=6.2 Hz, 1H), 4.13-4.00 (m, 4H), 3.82 (t,J=5.1 Hz, 1H), 3.36 (s, 3H), 3.00 (s, 3H)

Preparation of (Example 3 monomer): To a mixture of 5 (3 g, 8.54 mmol)and DIEA (2.21 g, 17.08 mmol, 2.97 mL) in ACN (90 mL) was added P2 (3.03g, 12.81 mmol) dropwise at 15° C. The reaction mixture was stirred at15° C. for 5 h. Upon completion, the reaction mixture was diluted withEA (40 mL) and quenched with 5% NaHCO₃ (20 mL). The organic layer waswashed with brine (30 mL), dried over Na₂SO₄, filtered and evaporated togive a residue. The residue was purified by flash silica gelchromatography (ISCO®; 12 g SepaFlash® Silica Flash Column, Eluent of0˜15% i-PrOH/(DCM with 2% TEA) gradient @ 20 mL/min) to Example 3monomer (2.1 g, 43.93% yield) as a white solid. ESI-LCMS: 552.3 [M+H]⁺;¹H NMR (400 MHz, CD₃CN) δ=8.78 (br s, 1H), 7.57 (dd, J=4.6, 8.2 Hz, 1H),5.97-5.80 (m, 1H), 5.67 (d, J=8.3 Hz, 1H), 4.46-4.11 (m, 4H), 3.95-3.58(m, 5H), 3.44 (d, J=16.3 Hz, 3H), 3.02 (d, J=7.5 Hz, 3H), 2.73-2.59 (m,2H), 1.23-1.15 (m, 12H); ³¹P NMR (162 MHz, CD₃CN) δ=150.30, 150.10

Example 4: Synthesis of 5′ End Cap Monomer

Example 4 Monomer Synthesis Scheme

Preparation of (2): To the solution of 1 (5 g, 12.90 mmol) and TEA (1.57g, 15.48 mmol, 2.16 mL) in DCM (50 mL) was added P-4 (2.24 g, 15.48mmol, 1.67 mL) in DCM (10 mL) dropwise at 15° C. under N₂. The reactionmixture was stirred at 15° C. for 3 h. Upon completion as monitored byLCMS and TLC (PE:EtOAc=0:1), the reaction mixture was concentrated todryness, diluted with H₂O (20 mL), and extracted with EA (50 mL*3). Thecombined organic layers were washed with brine (30 mL*3), dried overanhydrous Na₂SO₄, filtered, and the filtrate was concentrated underreduced pressure to give a residue. The residue was purified by flashsilica gel chromatography (ISCO®; 40 g SepaFlash® Silica Flash Column,Eluent of 0˜95% Ethyl acetate/Petroleum ether gradient @ 60 mL/min) togive 2 (5.3 g, 71.3% yield) as a white solid. ESI-LCMS: 496.1 [M+H]⁺; HNMR (400 MHz, CDCl₃) δ=0.10 (d, J=4.02 Hz, 6H) 0.91 (s, 9H) 3.42-3.54(m, 3H) 3.65-3.70 (m, 1H) 3.76-3.89 (m, 6H) 4.00 (dd, J=10.92, 2.89 Hz,1H) 4.08-4.13 (m, 1H) 4.15-4.23 (m, 2H) 5.73 (dd, J=8.28, 2.01 Hz, 1H)5.84 (d, J=2.76 Hz, 1H) 6.86 (d, J=15.81 Hz, 1H) 7.72 (d, J=8.03 Hz, 1H)9.10 (s, 1H); ³¹P NMR (162 MHz, CD₃CN) δ=9.65

Preparation of (3): To a solution of 2 (8.3 g, 16.75 mmol) in THF (50mL) were added TBAF (1 M, 16.75 mL) and CH₃COOH (1.01 g, 16.75 mmol,957.95 uL). The mixture was stirred at 20° C. for 12 hr. Upon completionas monitored by LCMS, the reaction mixture was concentrated underreduced pressure. The residue was purified by column chromatography(SiO₂, PE: EA=0˜100%; MeOH/EA=0˜10%) to give 3 (5 g, 77.51% yield) as awhite solid. ESI-LCMS: 382.1 [M+H]⁺; ¹H NMR (400 MHz, CDCl₃) δ=3.35 (s,3H) 3.65 (br d, J=2.76 Hz, 3H) 3.68 (d, J=2.76 Hz, 3H) 3.77 (t, J=5.08Hz, 1H) 3.84-4.10 (m, 4H) 5.33 (br d, J=5.52 Hz, 1H) 5.62 (d, J=7.77 Hz,1H) 5.83 (d, J=4.94 Hz, 1H) 7.69 (d, J=7.71 Hz, 1H) 9.08 (d, J=16.81 Hz,1H) 11.39 (br s, 1H); ³¹P NMR (162 MHz, CD₃CN) δ=15.41

Preparation of (Example 4 monomer): To a solution of 3 (2 g, 5.25 mmol)and DIPEA (2.03 g, 15.74 mmol, 2.74 mL, 3 eq) in MeCN (21 mL) andpyridine (7 mL) was added P2 (1.86 g, 7.87 mmol) dropwise at 20° C., andthe mixture was stirred at 20° C. for 3 hr. Upon completion as monitoredby LCMS, the reaction mixture was diluted with water (20 mL) andextracted with EA (50 mL). The combined organic layers were washed withbrine (30 mL), dried over anhydrous Na₂SO₄, filtered, and the filtratewas concentrated under reduced pressure to give a residue. The residuewas purified by flash silica gel chromatography (ISCO®; 25 g SepaFlash®Silica Flash Column, Eluent of 0˜45% (Ethyl acetate:EtOH=4:1)/Petroleumether gradient) to give Example 4 monomer (1.2 g, 38.2% yield) as awhite solid. ESI-LCMS: 604.1 [M+H]⁺; ¹H NMR (400 MHz, CD₃CN) δ=1.12-1.24(m, 12H) 2.61-2.77 (m, 2H) 3.43 (d, J=17.64 Hz, 3H) 3.59-3.69 (m, 2H)3.71-3.78 (m, 6H) 3.79-4.14 (m, 5H) 4.16-4.28 (m, 1H) 4.29-4.42 (m, 1H)5.59-5.72 (m, 1H) 5.89 (t, J=4.53 Hz, 1H) 7.48 (br d, J=12.76 Hz, 1H)7.62-7.74 (m, 1H) 9.26 (br s, 1H); ³¹P NMR (162 MHz, CD₃CN) δ=150.57,149.96, 9.87

Example 5: Synthesis of 5′ End Cap Monomer

Example 5 Monomer Synthesis Scheme

Preparation of (2): To a solution of 1 (30 g, 101.07 mmol, 87% purity)in CH₃CN (1.2 L) and Py (60 mL) were added 12 (33.35 g, 131.40 mmol,26.47 mL) and PPh₃ (37.11 g, 141.50 mmol) in one portion at 10° C. Thereaction was stirred at 25° C. for 48 h. Upon completion, the mixturewas diluted with saturated aq.Na₂S₂O₃ (300 mL) and saturated aq.NaHCO₃(300 mL), concentrated to remove CH₃CN, and extracted with EtOAc (300mL*3). The combined organic layers were washed with brine (300 mL),dried over Na₂SO₄, filtered and concentrated under reduced pressure togive a residue. The residue was purified by flash silica gelchromatography (ISCO®; 330 g SepaFlash® Silica Flash Column, Eluent of0˜60% Methanol/Dichloromethane gradient @ 100 mL/min) to give 2 (28.2 g,72% yield) as a brown solid. ESI-LCMS: 369.1 [M+H]⁺; H NMR (400 MHz,DMSO-d₆) δ=11.43 (s, 1H), 7.68 (d, J=8.1 Hz, 1H), 5.86 (d, J=5.5 Hz,1H), 5.69 (d, J=8.1 Hz, 1H), 5.46 (d, J=6.0 Hz, 1H), 4.08-3.96 (m, 2H),3.90-3.81 (m, 1H), 3.60-3.51 (m, 1H), 3.40 (dd, J=6.9, 10.6 Hz, 1H),3.34 (s, 3H).

Preparation of (3): To the solution of 2 (12 g, 32.6 mmol) in DCM (150mL) were added AgNO₃ (11.07 g, 65.20 mmol), 2,4,6-trimethylpyridine(11.85 g, 97.79 mmol, 12.92 mL), and DMTCl (22.09 g, 65.20 mmol) at 10°C., and the reaction mixture was stirred at 10° C. for 16 hr. Uponcompletion, the mixture was filtered and the filtrate was concentratedunder reduced pressure. The residue was purified by flash silica gelchromatography (ISCO®; 120 g SepaFlash® Silica Flash Column, Eluent of0˜50% Ethyl acetate/Petroleum ether gradient @ 60 mL/min) to give 3 (17g, 70.78% yield) as a yellow solid. ESI-LCMS: 693.1 [M+Na]⁺¹; H NMR (400MHz, DMSO-d₆) δ=11.46 (s, 1H), 7.60 (d, J=8.4 Hz, 1H), 7.49 (d, J=7.2Hz, 2H), 7.40-7.30 (m, 6H), 7.29-7.23 (m, 1H), 6.93 (d, J=8.8 Hz, 4H),5.97 (d, J=6.0 Hz, 1H), 5.69 (d, J=8.0 Hz, 1H), 4.05-4.02 (m, 1H), 3.75(d, J=1.2 Hz, 6H), 3.57 (t, J=5.6 Hz, 1H), 3.27 (s, 4H), 3.06 (t, J=10.4Hz, 1H), 2.98-2.89 (m, 1H).

Preparation of (4): To a solution of 3 (17 g, 25.35 mmol) in DMF (200mL) was added AcSK (11.58 g, 101.42 mmol) at 25° C., and the reactionwas stirred at 60° C. for 2 hr. The mixture was diluted with H₂O (600mL) and extracted with EtOAc (300 mL*4). The combined organic layerswere washed with brine (300 mL), dried over Na₂SO₄, filtered, andconcentrated under reduced pressure to give 4 (15.6 g, crude) as a brownsolid, which was used directly without further purification. ESI-LCMS:641.3 [M+H]⁺.

Preparation of (5): To a solution of 4 (15.6 g, 25.21 mmol) in CH₃CN(200 mL) were added DTT (11.67 g, 75.64 mmol, 11.22 mL) and LiOH.H₂O(1.06 g, 25.21 mmol) at 10° C. under Ar. The reaction was stirred at 10°C. for 1 hr. The mixture was concentrated under reduced pressure toremove CH₃CN, and the residue was diluted with H₂O (400 mL) andextracted with EtOAc (200 mL*3). The combined organic layers were washedwith brine (300 mL), dried over Na₂SO₄, filtered and concentrated underreduced pressure to give a residue. The residue was purified by flashsilica gel chromatography (ISCO®; 220 g SepaFlash® Silica Flash Column,Eluent of 0˜60% Ethyl acetate/Petroleum ether gradient @ 100 mL/min) togive 5 (8.6 g, 56.78% yield) as a white solid. ESI-LCMS: 599.3 [M+Na]⁺;¹H NMR (400 MHz, DMSO-d₆) δ=8.79 (s, 1H), 7.61 (d, J=8.0 Hz, 1H),7.56-7.46 (m, 2H), 7.45-7.37 (m, 4H), 7.36-7.27 (m, 3H), 6.85 (dd,J=2.8, 8.8 Hz, 4H), 5.85 (d, J=1.3 Hz, 1H), 5.68 (dd, J=2.0, 8.2 Hz,1H), 4.33-4.29 (m, 1H), 3.91 (dd, J=4.8, 8.2 Hz, 1H), 3.81 (d, J=1.6 Hz,6H), 3.33 (s, 3H), 2.85-2.80 (m, 1H), 2.67-2.55 (m, 2H), 1.11 (t, J=8.8Hz, 1H).

Preparation of (Example 5 monomer): To a solution of 5 (6 g, 10.40 mmol)in DCM (120 mL) were added P1 (4.08 g, 13.53 mmol, 4.30 mL) and DCI(1.35 g, 11.45 mmol) in one portion at 10° C. under Ar. The reaction wasstirred at 10° C. for 2 hr. The reaction mixture was diluted withsaturated aq.NaHCO₃ (50 mL) and extracted with DCM (20 mL*3). Thecombined organic layers were washed with brine (30 mL), dried overNa₂SO₄, filtered and concentrated under reduced pressure to give aresidue. The residue was purified by prep-HPLC (column: YMC-Triart PrepC18 250*50 mm*10 um; mobile phase: [water (10 mM NH₄HCO₃)-ACN]; B %:35%-81%, 20 min) to give Example 5 monomer (3.54 g, 43.36% yield) as ayellow solid. ESI-LCMS: 776.4 [M+H]⁺; ¹H NMR (400 MHz, DMSO-d₆)δ=7.65-7.38 (m, 7H), 7.37-7.22 (m, 3H), 6.90 (d, J=8.4 Hz, 4H), 5.92 (s,1H), 5.66 (t, J=8.2 Hz, 1H), 4.13 (d, J=4.0 Hz, 1H), 4.00-3.88 (m, 1H),3.87-3.59 (m, 10H), 3.33 (d, J=5.8 Hz, 3H), 3.12-2.94 (m, 1H), 2.78-2.60(m, 3H), 2.55-2.48 (m, 1H), 1.36-0.98 (m, 12H); ³¹P NMR (162 MHz,DMSO-d₆) δ=162.69.

Example 6: Synthesis of 5′ End Cap Monomer

Example 6 Monomer Synthesis Scheme

Preparation of (2): To a solution of 1 (22.6 g, 45.23 mmol) in DCM (500mL) and H₂O (125 mL) were added TEMPO (6.40 g, 40.71 mmol) and DIB(29.14 g, 90.47 mmol) at 0° C. The mixture was stirred at 20° C. for 20h. Upon completion as monitored by LCMS, saturated aq. NaHCO₃ was addedto the mixture to adjust pH >8. The mixture was diluted with H₂O (200mL) and washed with DCM (100 mL*3). The aqueous layer was collected,adjusted to pH<5 by HCl (4M), and extracted with DCM (200 mL*3). Thecombined organic layers were washed with brine (300 mL), dried overNa₂SO₄, filtered, and concentrated under reduced pressure to give 2(17.5 g, 68.55% yield) as a yellow solid. ESI-LCMS: 514.2 [M+H]⁺; ¹H NMR(400 MHz, DMSO-d₆) δ=11.27 (s, 1H), 8.86 (s, 1H), 8.78 (s, 1H), 8.06 (d,J=7.5 Hz, 2H), 7.68-7.62 (m, 1H), 7.59-7.52 (m, 2H), 6.28 (d, J=6.8 Hz,1H), 4.82-4.76 (m, 1H), 4.54 (dd, J=4.1, 6.7 Hz, 1H), 4.48 (d, J=1.8 Hz,1H), 3.32 (s, 3H), 0.94 (s, 9H), 0.18 (d, J=4.8 Hz, 6H).

Preparation of (3): To a solution of 2 (9.3 g, 18.11 mmol) in MeOH (20mL) was added SOCl₂ (3.23 g, 27.16 mmol, 1.97 mL) dropwise at 0° C. Themixture was stirred at 20° C. for 0.5 hr. Upon completion as monitoredby LCMS, the reaction mixture was quenched by addition of saturated aq.NaHCO₃ (80 mL) and concentrated under reduced pressure to remove MeOH.The aqueous layer was extracted with DCM (80 mL*3). The combined organiclayers were washed with brine (200 mL), dried over Na₂SO₄, filtered andconcentrated under reduced pressure to give a residue. The residue waspurified by flash silica gel chromatography (ISCO®; 120 g SepaFlash®Silica Flash Column, Eluent of 0˜5%, MeOH/DCM gradient @ 85 mL/min) togive 3 (5.8 g, 60% yield) as a yellow solid. ESI-LCMS: 528.3 [M+H]⁺, ¹HNMR (400 MHz, DMSO-d₆) δ=11.28 (s, 1H), 8.79 (d, J=7.3 Hz, 2H), 8.06 (d,J=7.5 Hz, 2H), 7.68-7.62 (m, 1H), 7.60-7.53 (m, 2H), 6.28 (d, J=6.6 Hz,1H), 4.87 (dd, J=2.4, 4.0 Hz, 1H), 4.61 (dd, J=4.3, 6.5 Hz, 1H), 4.57(d, J=2.2 Hz, 1H), 3.75 (s, 3H), 3.32 (s, 3H), 0.94 (s, 9H), 0.17 (d,J=2.2 Hz, 6H).

Preparation of (4): To a mixture of 3 (5.7 g, 10.80 mmol) in CD₃OD (120mL) was added NaBD₄ (1.63 g, 43.21 mmol) in portions at 0° C., and themixture was stirred at 20° C. for 1 hr. Upon completion as monitored byLCMS, the reaction mixture was neutralized by AcOH (˜10 mL) andconcentrated under reduced pressure to give a residue. The residue waspurified by flash silica gel chromatography (ISCO®; 40 g SepaFlash®Silica Flash Column, Eluent of 0˜5%, MeOH/DCM gradient @ 40 mL/min) togive 4 (4.15 g, 7.61 mmol, 70.45% yield) as a yellow solid. ESI-LCMS:502.2 [M+H]⁺; ¹H NMR (400 MHz, DMSO-d₆) δ=11.23 (s, 1H), 8.76 (s, 2H),8.04 (d, J=7.3 Hz, 2H), 7.69-7.62 (m, 1H), 7.60-7.52 (m, 2H), 6.14 (d,J=6.0 Hz, 1H), 5.18 (s, 1H), 4.60-4.51 (m, 2H), 3.98 (d, J=3.0 Hz, 1H),3.32 (s, 3H), 0.92 (s, 9H), 0.13 (d, J=1.5 Hz, 6H).

Preparation of (5): To a solution of 4 (4.85 g, 9.67 mmol) in pyridine(50 mL) was added DMTrCl (5.90 g, 17.40 mmol) at 25° C. and the mixturewas stirred for 2 hr. Upon completion as monitored by LCMS, the reactionmixture was concentrated under reduced pressure to remove pyridine. Theresidue was diluted with EtOAc (150 mL) and washed with H₂O (50 mL*3),dried over Na₂SO₄, filtered and concentrated under reduced pressure togive a residue. The residue was purified by flash silica gelchromatography (ISCO®; 80 g SepaFlash® Silica Flash Column, Eluent of0˜70%, EA/PE gradient @ 60 mL/min) to give 5 (6.6 g, 84.06% yield) as ayellow solid. ESI-LCMS: 804.3[M+H]⁺, ¹H NMR (400 MHz, DMSO-d₆) δ=11.22(s, 1H), 8.68 (d, J=11.0 Hz, 2H), 8.03 (d, J=7.3 Hz, 2H), 7.68-7.60 (m,1H), 7.58-7.49 (m, 2H), 7.37-7.30 (m, 2H), 7.27-7.16 (m, 7H), 6.88-6.79(m, 4H), 6.17 (d, J=4.2 Hz, 1H), 4.72 (t, J=5.0 Hz, 1H), 4.60 (t, J=4.5Hz, 1H), 4.03-3.98 (m, 1H), 3.71 (s, 6H), 0.83 (s, 9H), 0.12-0.03 (m,6H).

Preparation of (6): To a solution of 5 (6.6 g, 8.21 mmol) in THF (16 mL)was added TBAF (1 M, 8.21 mL,), and the mixture was stirred at 20° C.for 2 hr. Upon completion as monitored by LCMS, the reaction mixture wasdiluted with EA (150 mL) and washed with H₂O (50 mL*3). The organiclayer was washed with brine (150 mL), dried over Na₂SO₄, filtered andconcentrated under reduced pressure to give a residue. The residue waspurified by flash silica gel chromatography (ISCO®; 80 g SepaFlash®Silica Flash Column, Eluent of 10-100%, EA/PE gradient @ 30 mL/min) togive 6 (5.4 g, 94.4% yield) as a yellow solid. ESI-LCMS: 690.3 [M+H]⁺;¹H NMR (400 MHz, DMSO-d₆) δ=11.24 (s, 1H), 8.69 (s, 1H), 8.62 (s, 1H),8.05 (d, J=7.3 Hz, 2H), 7.69-7.62 (m, 1H), 7.60-7.52 (m, 2H), 7.40-7.33(m, 2H), 7.30-7.18 (m, 7H), 6.84 (dd, J=5.9, 8.9 Hz, 4H), 6.19 (d, J=4.8Hz, 1H), 5.36 (d, J=6.0 Hz, 1H), 4.59-4.52 (m, 1H), 4.48 (q, J=5.1 Hz,1H), 4.11 (d, J=4.8 Hz, 1H), 3.72 (d, J=1.0 Hz, 6H), 3.40 (s, 3H).

Preparation of (Example 6 monomer): To a solution of 6 (8.0 g, 11.60mmol) in MeCN (150 mL) was added P-1 (4.54 g, 15.08 mmol, 4.79 mL) at 0°C., followed by DCI (1.51 g, 12.76 mmol) in one portion. The mixture waswarmed to 20° C. and stirred for 2 h. Upon completion as monitored byLCMS, the reaction mixture was quenched by addition of saturated aq.NaHCO₃ (50 mL) and diluted with DCM (250 mL). The organic layer waswashed with saturated aq.NaHCO₃ (50 mL*2), dried over Na₂SO₄, filteredand concentrated under reduced pressure. The residue was purified by aflash silica gel column (0% to 60% EA in PE contain 0.5% TEA) to giveExample 6 monomer (5.75 g, 55.37% yield, 99.4% purity) as a white solid.ESI-LCMS: 890.4 [M+H]⁺; ¹H NMR (400 MHz, CD₃CN) δ=9.55 (s, 1H),8.63-8.51 (m, 1H), 8.34-8.24 (m, 1H), 7.98 (br d, J=7.5 Hz, 2H),7.65-7.55 (m, 1H), 7.53-7.46 (m, 2H), 7.44-7.37 (m, 2H), 7.32-7.17 (m,7H), 6.84-6.77 (m, 4H), 6.14 (d, J=4.3 Hz, 1H), 4.84-4.73 (m, 1H),4.72-4.65 (m, 1H), 4.34-4.27 (m, 1H), 3.91-3.61 (m, 9H), 3.50-3.43 (m,3H), 2.72-2.61 (m, 1H), 2.50 (t, J=6.0 Hz, 1H), 1.21-1.15 (m, 10H), 1.09(d, J=6.8 Hz, 2H); ³¹P NMR (162 MHz, CD₃CN) δ =150.01, 149.65

Example 7: Synthesis of 5′ End Cap Monomer

Example 7 Monomer Synthesis Scheme

Preparation of (2): To a solution of 1 (10 g, 27.22 mmol) in CH₃CN (200mL) and H₂O (50 mL) were added TEMPO (3.85 g, 24.50 mmol) and DIB (17.54g, 54.44 mmol). The mixture was stirred at 25° C. for 12 h. Uponcompletion as monitored by LCMS, the reaction mixture was concentratedunder reduced pressure to give a residue. The residue was trituratedwith EtOAc (600 mL) for 30 min. The resulting suspension was filteredand the collected solid was washed with EtOAc (300 mL*2) to give 2(20.09 g, 91.5% yield) as a white solid. ESI-LCMS: 382.0 [M+H]⁺.

Preparation of (3): To a solution of 2 (6 g, 15.73 mmol) in MeOH (100mL) was added SOCl₂ (2.81 g, 23.60 mmol, 1.71 mL) dropwise at 0° C. Themixture was stirred at 25° C. for 12 h. Upon completion as monitored byLCMS, the reaction mixture was quenched by addition of NaHCO₃ (4 g) andstirred at 25° C. for 30 min. The reaction mixture was filtered and thefiltrate was concentrated under reduced pressure to give 3 (18.8 g,95.6% yield) as a white solid. The crude product was used for the nextstep without further purification. (The reaction was set up in parallel3 batches and combined). ESI-LCMS: 396.1 [M+H]⁺; ¹H NMR (400 MHz,DMSO-d₆) δ=12.26-11.57 (m, 2H), 8.42-8.06 (m, 1H), 6.14-5.68 (m, 2H),4.56 (s, 2H), 4.33 (dd, J=4.0, 7.3 Hz, 1H), 3.77 (m, 3H), 3.30 (s, 3H),2.81-2.69 (m, 1H), 1.11 (s, 6H)

Preparation of (4 & 5): To a mixture of 3 (10.1 g, 25.55 mmol) in CD₃OD(120 mL) was added NaBD₄ (3.29 g, 86.86 mmol, 3.4 eq) in portions at 0°C. The mixture was stirred at 25° C. for 1 h. Upon completion asmonitored by LCMS, the reaction mixture was neutralized with AcOH (˜15mL) and concentrated under reduced pressure to give a residue. Theresidue was purified by flash silica gel chromatography (ISCO®; 120 gSepaFlash® Silica Flash Column, Eluent of 0˜7.4%, MeOH/DCM gradient @ 80mL/min) to give 4 (2.98 g, 6.88 mmol, 27% yield) as a yellow solid.ESI-LCMS: 370.1[M+H]⁺ and 5 (10.9 g, crude) as a yellow solid. ESI-LCMS:300.1[M+H]⁺; ¹H NMR (400 MHz, CD₃OD) δ=7.85 (s, 1H), 5.87 (d, J=6.0 Hz,1H), 4.46-4.39 (m, 1H), 4.34 (t, J=5.4 Hz, 1H), 4.08 (d, J=3.1 Hz, 1H),3.49-3.38 (m, 4H)

Preparation of 6: To a solution of 4 (1.9 g, 4.58 mmol, 85.7% purity) inpyridine (19 mL) was added DMTrCl (2.02 g, 5.96 mmol). The mixture wasstirred at 25° C. for 2 h under N₂. Upon completion as monitored byLCMS, the reaction mixture was quenched by MeOH (10 mL) and concentratedunder reduce pressure to give a residue. The residue was diluted withH₂O (10 mL*3) and extracted with EA (20 mL*3). The combined organiclayers were washed with brine (20 mL), dried over anhydrous Na₂SO₄,filtered and concentrated under reduce pressure to give a residue. Theresidue was purified by flash silica gel chromatography (ISCO®; 25 gSepaFlash® Silica Flash Column, Eluent of 0˜77%, PE: (EA with 10% EtOH):1% TEA@ 35 mL/min) to give 6 (2.6 g, 81.71% yield, 96.71% purity) as awhite foam. ESI-LCMS: 672.2 [M+H]⁺; ¹H NMR (400 MHz, CDCl₃) δ=12.02 (s,1H), 7.96 (s, 1H), 7.83 (s, 1H), 7.51 (d, J=7.4 Hz, 2H), 7.37 (d, J=8.6Hz, 4H), 7.25-7.17 (m, 2H), 6.80 (t, J=8.4 Hz, 4H), 5.88 (d, J=6.3 Hz,1H), 4.69 (t, J=5.7 Hz, 1H), 4.64 (s, 1H), 4.54 (s, 1H), 4.19 (d, J=2.9Hz, 1H), 3.77 (d, J=4.5 Hz, 6H), 3.60-3.38 (m, 3H), 2.81 (s, 1H), 1.81(td, J=6.9, 13.7 Hz, 1H), 0.97 (d, J=6.8 Hz, 3H), 0.80 (d, J=6.9 Hz, 3H)

Preparation of Example 7 monomer: To a solution of 6 (8.4 g, 12.5 mmol)in MeCN (80 mL) was added P-1 (4.9 g, 16.26 mmol, 5.16 mL) at 0° C.,followed by addition of DCI (1.624 g, 13.76 mmol) in one portion at 0°C. under Ar. The mixture was stirred at 25° C. for 2 h. Upon completionas monitored by LCMS, the reaction mixture was quenched with saturatedaq.NaHCO₃ (20 mL) and extracted with DCM (50 mL*2). The combined organiclayers were dried over anhydrous Na₂SO₄, filtered and concentrated underreduce pressure to give a residue. The residue was purified by flashsilica gel chromatography (ISCO®; 40 g SepaFlash® Silica Flash Column,Eluent of 0˜52% PE: EA (10% EtOH): 5% TEA, @ 80 mL/min) to give Example7 monomer (3.4 g, 72.1% yield,) as a white foam. ESI-LCMS: 872.4 [M+H]⁺;¹H NMR (400 MHz, CD₃CN) δ=12.46-11.07 (m, 1H), 9.29 (s, 1H), 7.84 (d,J=14.6 Hz, 1H), 7.42 (t, J=6.9 Hz, 2H), 7.34-7.17 (m, 7H), 6.85-6.77 (m,4H), 5.95-5.77 (m, 1H), 4.56-4.40 (m, 2H), 4.24 (dd, J=4.0, 13.3 Hz,1H), 3.72 (d, J=2.0 Hz, 7H), 3.66-3.53 (m, 3H), 3.42 (d, J=11.8 Hz, 3H),2.69-2.61 (m, 1H), 2.60-2.42 (m, 2H), 1.16-1.00 (m, 18H); ³¹P NMR (162MHz, CD₃CN) δ=149.975, 149.9

Example 8: Synthesis of 5′ End Cap Monomer

Example 8 Monomer Synthesis Scheme

Preparation of (2): To a solution of 1 (40 g, 58.16 mmol) in DMF (60 mL)were added imidazole (11.88 g, 174.48 mmol), NaI (13.08 g, 87.24 mmol),and TBSCl (17.52 g, 116.32 mmol) at 20° C. in one portion. The reactionmixture was stirred at 20° C. for 12 h. Upon completion, the mixture wasdiluted with EA (200 mL). The organic layer was washed with brine/water(80 mL/80 mL*4), dried over Na₂SO₄, filtered and evaporated to give 2(50.8 g, crude) as yellow solid. ESI-LCMS: 802.3 [M+H]⁺

Preparation of (3): To a solution of 2 (8.4 g, 10.47 mmol) in DCM (120mL) were added Et₃SiH (3.06 g, 26.3 mmol, 4.2 mL) and TFA (1.29 g, 0.84mL) dropwise at 0° C. The reaction mixture was stirred at 20° C. for 2h. The reaction mixture was washed with saturated aq.NaHCO₃ (15 mL) andbrine (80 mL). The organic layer was dried over Na₂SO₄, filtered andevaporated. The residue was purified by flash silica gel chromatography(ISCO®; 80 g SepaFlash® Silica Flash Column, Eluent of 0˜83% EA/PEgradient @ 80 mL/min) to give 3 (2.92 g, 55.8% yield,) as a white solid.ESI-LCMS: 500.2 [M+H]⁺; ¹H NMR (400 MHz, CDCl₃) δ=8.79 (s, 1H), 8.14 (s,1H), 8.02 (d, J=7.6 Hz, 2H), 7.64-7.58 (m, 1H), 7.56-7.49 (m, 2H),5.98-5.93 (m, 1H), 4.63-4.56 (m, 2H), 4.23 (s, 1H), 3.98 (dd, J=1.5,13.1 Hz, 1H), 3.75 (dd, J=1.5, 13.1 Hz, 1H), 3.28 (s, 3H), 2.06-1.99 (m,1H), 1.00-0.90 (m, 9H), 0.15 (d, J=7.0 Hz, 6H).

Preparation of (4): 3 (6 g, 12.01 mmol) and tert-butylN-methylsulfonylcarbamate (3.52 g, 18.01 mmol) were co-evaporated withtoluene (50 mL), dissolved in dry THF (100 mL), and cooled to 0° C. PPh₃(9.45 g, 36.03 mmol,) was then added, followed by dropwise addition ofDIAD (7.28 g, 36.03 mmol, 7.00 mL) in dry THF (30 mL). The reactionmixture was stirred at 20° C. for 18 h. Upon completion, the reactionmixture was then diluted with DCM (100 mL) and washed with water (70 mL)and brine (70 mL), dried over Na₂SO₄, filtered and evaporated to give aresidue. The residue was purified by flash silica gel chromatography(ISCO®; 80 g SepaFlash® Silica Flash Column, Eluent of 0˜100% Ethylacetate/Petroleum ether gradient @ 60 mL/min) followed by reverse-phaseHPLC (0.1% NH₃.H₂O condition, eluent at 74%) to give 4 (2.88 g, 25%yield) as a white solid. ESI-LCMS: 677.1 [M+H]⁺; ¹H NMR (400 MHz, CDCl₃)δ=9.24 (s, 1H), 8.84 (s, 1H), 8.36 (s, 1H), 8.05 (br d, J=7.3 Hz, 2H),7.66-7.42 (m, 4H), 6.16 (d, J=5.0 Hz, 1H), 4.52 (br t, J=4.5 Hz, 1H),4.25-4.10 (m, 1H), 3.97 (br dd, J=8.0, 14.8 Hz, 1H), 3.48 (s, 3H), 3.27(s, 3H), 1.54 (s, 9H), 0.95 (s, 9H), 0.14 (d, J=0.8 Hz, 6H).

Preparation of (5): To a solution of 4 (2.8 g, 4.14 mmol) in THF (20 mL)was added TBAF (4 M, 1.03 mL) and the mixture was stirred at 20° C. for12 h. The reaction mixture was then evaporated. The residue was purifiedby flash silica gel chromatography (ISCO®; 12 g SepaFlash® Silica FlashColumn, Eluent of 0˜6% MeOH/ethyl acetate gradient @ 20 mL/min) to give5 (2.1 g, 83.92% yield) as a white solid. ESI-LCMS: 563.1[M+H]⁺; ¹H NMR(400 MHz, CDCl₃) δ=8.85-8.77 (m, 1H), 8.38 (s, 1H), 8.11-7.99 (m, 2H),7.64-7.50 (m, 4H), 6.19 (d, J=2.8 Hz, 1H), 4.36-4.33 (m, 1H), 4.29 (brd, J=4.3 Hz, 1H), 4.22-4.02 (m, 2H), 3.65-3.59 (m, 3H), 3.28 (s, 3H),1.54 (s, 9H).

Preparation of (6): To a solution of 5 (2.1 g, 3.73 mmol) in DCM (20 mL)was added TFA (7.70 g, 67.53 mmol, 5 mL) at 0° C. The reaction mixturewas stirred at 20° C. for 24 h. Upon completion, the reaction wasquenched with saturated aq. NaHCO₃ to reach pH 7. The organic layer wasdried over Na₂SO₄, filtered, and evaporated at low pressure. The residuewas purified by flash silica gel chromatography (ISCO®; 12 g SepaFlash®Silica Flash Column, Eluent of 0˜7% DCM/MeOH gradient @ 20 mL/min) togive 1.6 g (impure, 75% LCMS purity), followed by prep-HPLC [FAcondition, column: Boston Uni C18 40*150*5 um; mobile phase: [water(0.225% FA)-ACN]; B %: 8%-38%, 7.7 min.] to give 6 (1.04 g, 63.7% yield)as a white solid. ESI-LCMS: 485.0 [M+Na]⁺; ¹H NMR (400 MHz, DMSO-d₆)δ=11.27-11.21 (m, 1H), 8.77 (s, 1H), 8.74 (s, 1H), 8.05 (d, J=7.3 Hz,2H), 7.68-7.62 (m, 1H), 7.59-7.53 (m, 2H), 7.39 (t, J=6.3 Hz, 1H), 6.16(d, J=6.0 Hz, 1H), 5.48 (d, J=5.5 Hz, 1H), 4.55 (t, J=5.5 Hz, 1H),4.43-4.37 (m, 1H), 4.08-4.02 (m, 1H), 3.41-3.36 (m, 1H), 3.35 (s, 3H),3.31-3.22 (m, 1H), 2.91 (s, 3H).

Preparation of (Example 8 monomer): To a solution of 6 (1 g, 2.16 mmol)in DCM (30 mL) was added P1 (977.58 mg, 3.24 mmol, 1.03 mL), followed byDCI (306.43 mg, 2.59 mmol) at 0° C. in one portion under Ar atmosphere.The mixture was degassed and purged with Ar for 3 times, warmed to 20°C., and stirred for 2 hr under Ar atmosphere. Upon completion asmonitored by LCMS and TLC (PE:EtOAc=4:1), the reaction mixture wasdiluted with sat.aq. NaHCO₃ (30 mL) and extracted with DCM (50 mL*2).The combined organic layers were dried over anhydrous Na₂SO₄, filtered,and the filtrate was concentrated under reduced pressure to give aresidue. The crude product was purified by reversed-phase HPLC (40 g C18column: neutral condition, Eluent of 0˜57% of 0.3% NH₄HCO₃ in H₂O/CH₃CNether gradient @ 35 mL/min) to give Example 8 monomer (0.49 g, 33.7%yield) as a white solid. ESI-LCMS: 663.1[M+H]⁺; ¹H NMR (400 MHz, CD₃CN)δ=1.19-1.29 (m, 12H) 2.71 (q, J=5.77 Hz, 2H) 2.94 (d, J=6.27 Hz, 3H)3.35 (d, J=15.56 Hz, 3H) 3.40-3.52 (m, 2H) 3.61-3.97 (m, 4H) 4.23-4.45(m, 1H) 4.55-4.74 (m, 2H) 6.02 (dd, J=10.67, 6.40 Hz, 1H) 7.25 (br s,1H) 7.47-7.57 (m, 2H) 7.59-7.68 (m, 1H) 8.01 (d, J=7.78 Hz, 2H) 8.28 (s,1H) 8.66 (s, 1H) 9.69 (br s, 1H); ³¹P NMR (162 MHz, CD₃CN) δ=150.92,149.78.

Example 9: Synthesis of 5′-stabilized End Cap Modified Oligonucleotides

This example provides an exemplary method for synthesizing the siNAscomprising a 5′-stabilized end caps disclosed herein. The 5′-stabilizedend cap and/or deuterated phosphoramidites were dissolved in anhydrousacetonitrile and oligonucleotide synthesis was performed on a Expedite8909 Synthesizer using standard phosphoramidite chemistry. An extendedcoupling (12 minutes) of 0.12 M solution of phosphoramidite in anhydrousCH₃CN in the presence of Benzyl-thio-tetrazole (BTT) activator to asolid bound oligonucleotide followed by standard capping, oxidation andsulfurization produced modified oligonucleotides. The 0.02 M 12, THE:Pyridine; Water 7:2:1 was used as an oxidizing agent, while DDTT(dimethylamino-methylidene) amino)-3H-1,2,4-dithiazaoline-3-thione wasused as the sulfur-transfer agent for the synthesis ofoligoribonucleotide with a phosphorothioate backbone. The stepwisecoupling efficiency of all modified phosphoramidites was achieved around98%. After synthesis the solid support was heated with aqueous ammonia(28%) solution at 45° C. for 16 h or 0.05 M K₂CO₃ in methanol was usedto deprotect the base labile protecting groups. The crudeoligonucleotides were precipitated with isopropanol and centrifuged(Eppendorf 5810R, 3000 g, 4° C., 15 min) to obtain a pellet. The crudeproduct was then purified using ion exchange chromatography (TSK gelcolumn, 20 mM NaH₂PO₄, 10% CH₃CN, 1 M NaBr, gradient 20-60% B over 20column volumes) and fractions were analyzed by ion change chromatographyon an HPLC. Pure fractions were pooled and desalted by Sephadex G-25column and evaporated to dryness. The purity and molecular weight weredetermined by HPLC analysis and ESI-MS analysis. Single strand RNAoligonucleotides (sense and antisense strand) were annealed (1:1 bymolar equivalents) at 90° C. for 3 min followed by RT 40 min) to producethe duplexes.

Example 10: SARS-CoV-2-Nanoluc Antiviral Assay in Human ACE-2 ExpressingA549 Cells

The assay has been modified from Xie X et al., 2020, NatureCommunications, doi.org/10.1038/s41467-020-19055-7.

A549 cells stably expressing human ACE2 were grown in culture mediumconsisting of high-glucose DMEM supplemented with 10% fetal bovineserum, 1% penicillin/streptomycin, 1% HEPES and 10 μg/mL Blasticidin S.Cells were grown at 37° C. with 5% CO₂. All culture medium andantibiotics were purchased from ThermoFisher Scientific (Waltham,Mass.). SARS-CoV-2-Nluc virus was generated through inserting thenanoluciferase gene into the ORF7 gene of the infectious cDNA cloneSARS-CoV-2 virus (strain 2019-nCoV/USA_WA1/2020). For SARS-CoV-2-Nlucantiviral assay, A549-hACE2 cells (12,000 cells per well in 50 ulphenol-red free medium containing 2% FBS) were plated into white opaque96-well plate (purchased from Corning, Corning, N.Y.). On the next day,50 ul SARS-CoV-2-Nluc virus (MOI 0.08) was added to the cells, andincubated at 37° C. with 5% CO₂ for 3 hours. Oligonucleotides werediluted in Opti-MEM medium and mixed with equal volume of dilutedtransfection reagent RNAiMaX (0.2 ul/well) (ThermoFisher). Thetransfection mixture was incubated at room temperature for 10 mins andthen added to cell plate at 3 hr post infection (20 ul/well). 48 hr postinfection, 60 μL Nano luciferase substrate (Promega<Madison, Wis.) wereadded to each well. Luciferase signals were measured using a Synergy™Neo2 microplate reader (BioTek, Winooski, Vt.). Antiviral % inhibitionwas calculated as follows: [(Oligonucleotide treated cells infectedsample)−(no oligonucleotide infected control)]/[(Uninfected control)−(nooligonucleotide infected control)]*100; Using GraphPad (San Diego,Calif.) prism software version 8.3.1, the antiviral dose-response plotwas generated as a sigmoidal fit, log(inhibitor) vs response-variableslope (four parameters) model and the EC₅₀ was calculated which is thepredicted oligonucleotide concentration corresponding to a 50%inhibition of the viral cytopathic effect.

Results for siNA assessed with this assay are shown in Table 4 at theend of the specification in column labeled “SARS-CoV-2 nanoluc hACE-2A549 assay”.

Example 11: Three Concentration Reporter Plasmid Luciferase andCytotoxicity Assay in COS-7 Cells

COS-7 monkey fibroblast cells (ATCC, CRL-1651) were seeded into 96-wellculture plates at 15.0×10⁴ cells/well and cultured in Dulbecco'sModified Eagle's Medium (DMEM; Hyclone, SH30022) supplemented with 10%fetal bovine serum (FBS; Sigma-Aldrich, F4135) and 1%Penicillin-Streptomycin (P/S; Corning, 30-002-CI) at 37° C. and 5% CO₂.After 6 hrs of incubation, cells were transiently transfected withpsiCHECK2-SARS-CoV-2 plasmid (custom-synthesized by Genscript) at 50ng/well using 0.3 μL of Lipofectamine 3000 transfection reagent (1:1reagent/psi-CHECK2-SARS-CoV-2 DNA ratio; Invitrogen) in Opti-MEM(Invitrogen, 11058-021) according to the manufacturer's protocol. Afterovernight incubation, the medium was removed and replaced with 100 ulfresh growth media. Test siRNAs along with appropriate controls (AmbionsiRNAs, ThermoFisher) were diluted to final concentration of 1, 10 or100 nM in Opti-MEM (Invitrogen, 11058-021). Cells were then transfectedwith test siRNAs in duplicates using 0.3 ul/well RNAiMAX transfectionreagent (1:1 ratio; Invitrogen) according to the manufacturer'sprotocol. After approximately 48 hrs, the culture plates wereequilibrated to RT, 100 μL of Dual-Luciferase Reporter Assay reagent(Promega, E6120) were added to each well according to manufacturer'sprotocol. Luminescence was measured on an Envision plate reader (PerkinElmer). The results were then quantified by calculating the ratio ofrenilla to firefly luciferase expression for each of the duplicates andreported as percent inhibition of luciferase activity relative tono-drug control (mock transfection with psiCHECK2-SARS-CoV-2 plasmid).The assay was repeated with a different set of plates and cytotoxicityof test siRNAs was assessed 48 hrs post treatment of COS-7 cells. Thecells were lysed and assayed with Cell-Titer Glo reagent (Promega)according to the manufacturer's protocol.

Results for siNA assessed with this assay are shown in Table 4 at theend of the specification in column labeled “pSiCHECK-2 reporter assayCos-7 at least 50% inhibition”. The data was reported as % viabilityrelative to no-drug control (mock transfection with psiCHECK2-SARS-CoV-2plasmid).

Example 12: Reporter Plasmid Luciferase and Cytotoxicity Assay in Cos7Cells

COS-7 monkey fibroblast cells (ATCC, CRL-1651) were seeded into 96-wellculture plates at 15.0×10⁴ cells/well and cultured in Dulbecco'sModified Eagle's Medium (DMEM; Hyclone, SH30022) supplemented with 10%fetal bovine serum (FBS; Sigma-Aldrich, F4135) and 1%Penicillin-Streptomycin (P/S; Corning, 30-002-CI) at 37° C. and 5% CO₂.After 6 hrs of incubation, cells were transiently transfected withpsiCHECK2-SARS-CoV-2 plasmid (custom-synthesized by Genscript) at 50ng/well using 0.3 μL of Lipofectamine 3000 transfection reagent (1:1reagent/psi-CHECK2-SARS-CoV-2 DNA ratio; Invitrogen) in Opti-MEM(Invitrogen, 11058-021) according to the manufacturer's protocol. Afterovernight incubation, the medium was removed and replaced with 100 ulfresh growth media. Test siRNAs along with appropriate controls (AmbionsiRNAs, ThermoFisher) were serially diluted in Opti-MEM (Invitrogen,11058-021). Cells were then transfected with test siRNAs in duplicatesusing 0.3 ul/well RNAiMAX transfection reagent (1:1 ratio; Invitrogen)according to the manufacturer's protocol. After approximately 48 hrs,the culture plates were equilibrated to RT, 100 μL of Dual-LuciferaseReporter Assay reagent (Promega, E6120) were added to each wellaccording to manufacturer's protocol. Luminescence was measured on anEnvision plate reader (Perkin Elmer). The results were then quantifiedby calculating the ratio of renilla to firefly luciferase expression foreach of the duplicates and reported as percent inhibition of luciferaseactivity relative to no-drug control (mock transfection withpsiCHECK2-SARS-CoV-2 plasmid) and dose-response curves were fitted bynon-linear regression with variable slope (four parameters). Statisticalanalysis was performed in GraphPad Prism 8.3.1 (San Diego, Calif.) andthe EC₅₀ was calculated which is the predicted oligonucleotideconcentration corresponding to a 50% inhibition of the luciferaseactivity. The assay was repeated with a different set of plates andcytotoxicity of test siRNAs was assessed 48 hrs post treatment of COS-7cells. The cells were lysed and assayed with Cell-Titer Glo reagent(Promega) according to the manufacturer's protocol.

Results for siNA assessed with this assay are shown in Table 4 at theend of the specification in column labeled “pSiCHECK-2 reporter assayCos-7”. The data was reported as % viability relative to no-drug control(mock transfection with psiCHECK2-SARS-CoV-2 plasmid) and dose-responsecurves were fitted by non-linear regression with variable slope (fourparameters) using GraphPad prism software version 8.3.1.

All patents and publications mentioned in the specification areindicative of the levels of those of ordinary skill in the art to whichthe disclosure pertains. All patents and publications are hereinincorporated by reference to the same extent as if each individualpublication was specifically and individually indicated to beincorporated by reference.

Further, one skilled in the art readily appreciates that the presentdisclosure is well adapted to carry out the objects and obtain the endsand advantages mentioned, as well as those inherent therein.Modifications therein and other uses will occur to those skilled in theart. These modifications are encompassed within the spirit of thedisclosure and are defined by the scope of the claims, which set forthnon-limiting embodiments of the disclosure.

TABLE 1 Oligonucleotide Target Sequences SEQ Target SEQ Target reverseStart on End on ID forward sequence ID complement sequence Alias targettarget NO (sense strand) NO (antisense strand) 19-Mer Target SequencesNC_045512.2_19mer_win1_00190 190 208 1 CTGCTTACGGTTTCGTCCG 1204CGGACGAAACCGTAAGCAG NC_045512.2_19mer_win1_00191 191 209 2TGCTTACGGTTTCGTCCGT 1205 ACGGACGAAACCGTAAGCANC_045512.2_19mer_win1_00192 192 210 3 GCTTACGGTTTCGTCCGTG 1206CACGGACGAAACCGTAAGC NC_045512.2_19mer_win1_00193 193 211 4CTTACGGTTTCGTCCGTGT 1207 ACACGGACGAAACCGTAAGNC_045512.2_19mer_win1_00194 194 212 5 TTACGGTTTCGTCCGTGTT 1208AACACGGACGAAACCGTAA NC_045512.2_19mer_win1_00195 195 213 6TACGGTTTCGTCCGTGTTG 1209 CAACACGGACGAAACCGTANC_045512.2_19mer_win1_00196 196 214 7 ACGGTTTCGTCCGTGTTGC 1210GCAACACGGACGAAACCGT NC_045512.2_19mer_win1_00197 197 215 8CGGTTTCGTCCGTGTTGCA 1211 TGCAACACGGACGAAACCGNC_045512.2_19mer_win1_00198 198 216 9 GGTTTCGTCCGTGTTGCAG 1212CTGCAACACGGACGAAACC NC_045512.2_19mer_win1_00233 233 251 10CTAGGTTTCGTCCGGGTGT 1213 ACACCCGGACGAAACCTAGNC_045512.2_19mer_win1_00234 234 252 11 TAGGTTTCGTCCGGGTGTG 1214CACACCCGGACGAAACCTA NC_045512.2_19mer_win1_00235 235 253 12AGGTTTCGTCCGGGTGTGA 1215 TCACACCCGGACGAAACCTNC_045512.2_19mer_win1_00236 236 254 13 GGTTTCGTCCGGGTGTGAC 1216GTCACACCCGGACGAAACC NC_045512.2_19mer_win1_00237 237 255 14GTTTCGTCCGGGTGTGACC 1217 GGTCACACCCGGACGAAACNC_045512.2_19mer_win1_00238 238 256 15 TTTCGTCCGGGTGTGACCG 1218CGGTCACACCCGGACGAAA NC_045512.2_19mer_win1_00239 239 257 16TTCGTCCGGGTGTGACCGA 1219 TCGGTCACACCCGGACGAANC_045512.2_19mer_win1_00240 240 258 17 TCGTCCGGGTGTGACCGAA 1220TTCGGTCACACCCGGACGA NC_045512.2_19mer_win1_00241 241 259 18CGTCCGGGTGTGACCGAAA 1221 TTTCGGTCACACCCGGACGNC_045512.2_19mer_win1_00242 242 260 19 GTCCGGGTGTGACCGAAAG 1222CTTTCGGTCACACCCGGAC NC_045512.2_19mer_win1_00243 243 261 20TCCGGGTGTGACCGAAAGG 1223 CCTTTCGGTCACACCCGGANC_045512.2_19mer_win1_00244 244 262 21 CCGGGTGTGACCGAAAGGT 1224ACCTTTCGGTCACACCCGG NC_045512.2_19mer_win1_00245 245 263 22CGGGTGTGACCGAAAGGTA 1225 TACCTTTCGGTCACACCCGNC_045512.2_19mer_win1_00246 246 264 23 GGGTGTGACCGAAAGGTAA 1226TTACCTTTCGGTCACACCC NC_045512.2_19mer_win1_00247 247 265 24GGTGTGACCGAAAGGTAAG 1227 CTTACCTTTCGGTCACACCNC_045512.2_19mer_win1_00248 248 266 25 GTGTGACCGAAAGGTAAGA 1228TCTTACCTTTCGGTCACAC NC_045512.2_19mer_win1_00249 249 267 26TGTGACCGAAAGGTAAGAT 1229 ATCTTACCTTTCGGTCACANC_045512.2_19mer_win1_00250 250 268 27 GTGACCGAAAGGTAAGATG 1230CATCTTACCTTTCGGTCAC NC_045512.2_19mer_win1_00251 251 269 28TGACCGAAAGGTAAGATGG 1231 CCATCTTACCTTTCGGTCANC_045512.2_19mer_win1_00252 252 270 29 GACCGAAAGGTAAGATGGA 1232TCCATCTTACCTTTCGGTC NC_045512.2_19mer_win1_00253 253 271 30ACCGAAAGGTAAGATGGAG 1233 CTCCATCTTACCTTTCGGTNC_045512.2_19mer_win1_00254 254 272 31 CCGAAAGGTAAGATGGAGA 1234TCTCCATCTTACCTTTCGG NC_045512.2_19mer_win1_00255 255 273 32CGAAAGGTAAGATGGAGAG 1235 CTCTCCATCTTACCTTTCGNC_045512.2_19mer_win1_00256 256 274 33 GAAAGGTAAGATGGAGAGC 1236GCTCTCCATCTTACCTTTC NC_045512.2_19mer_win1_00257 257 275 34AAAGGTAAGATGGAGAGCC 1237 GGCTCTCCATCTTACCTTTNC_045512.2_19mer_win1_00258 258 276 35 AAGGTAAGATGGAGAGCCT 1238AGGCTCTCCATCTTACCTT NC_045512.2_19mer_win1_00259 259 277 36AGGTAAGATGGAGAGCCTT 1239 AAGGCTCTCCATCTTACCTNC_045512.2_19mer_win1_00260 260 278 37 GGTAAGATGGAGAGCCTTG 1240CAAGGCTCTCCATCTTACC NC_045512.2_19mer_win1_00261 261 279 38GTAAGATGGAGAGCCTTGT 1241 ACAAGGCTCTCCATCTTACNC_045512.2_19mer_win1_00288 288 306 39 TCAACGAGAAAACACACGT 1242ACGTGTGTTTTCTCGTTGA NC_045512.2_19mer_win1_00289 289 307 40CAACGAGAAAACACACGTC 1243 GACGTGTGTTTTCTCGTTGNC_045512.2_19mer_win1_00290 290 308 41 AACGAGAAAACACACGTCC 1244GGACGTGTGTTTTCTCGTT NC_045512.2_19mer_win1_00291 291 309 42ACGAGAAAACACACGTCCA 1245 TGGACGTGTGTTTTCTCGTNC_045512.2_19mer_win1_00292 292 310 43 CGAGAAAACACACGTCCAA 1246TTGGACGTGTGTTTTCTCG NC_045512.2_19mer_win1_00293 293 311 44GAGAAAACACACGTCCAAC 1247 GTTGGACGTGTGTTTTCTCNC_045512.2_19mer_win1_00294 294 312 45 AGAAAACACACGTCCAACT 1248AGTTGGACGTGTGTTTTCT NC_045512.2_19mer_win1_00295 295 313 46GAAAACACACGTCCAACTC 1249 GAGTTGGACGTGTGTTTTCNC_045512.2_19mer_win1_00296 296 314 47 AAAACACACGTCCAACTCA 1250TGAGTTGGACGTGTGTTTT NC_045512.2_19mer_win1_00297 297 315 48AAACACACGTCCAACTCAG 1251 CTGAGTTGGACGTGTGTTTNC_045512.2_19mer_win1_00298 298 316 49 AACACACGTCCAACTCAGT 1252ACTGAGTTGGACGTGTGTT NC_045512.2_19mer_win1_00299 299 317 50ACACACGTCCAACTCAGTT 1253 AACTGAGTTGGACGTGTGTNC_045512.2_19mer_win1_00300 300 318 51 CACACGTCCAACTCAGTTT 1254AAACTGAGTTGGACGTGTG NC_045512.2_19mer_win1_00301 301 319 52ACACGTCCAACTCAGTTTG 1255 CAAACTGAGTTGGACGTGTNC_045512.2_19mer_win1_00302 302 320 53 CACGTCCAACTCAGTTTGC 1256GCAAACTGAGTTGGACGTG NC_045512.2_19mer_win1_00303 303 321 54ACGTCCAACTCAGTTTGCC 1257 GGCAAACTGAGTTGGACGTNC_045512.2_19mer_win1_00304 304 322 55 CGTCCAACTCAGTTTGCCT 1258AGGCAAACTGAGTTGGACG NC_045512.2_19mer_win1_00305 305 323 56GTCCAACTCAGTTTGCCTG 1259 CAGGCAAACTGAGTTGGACNC_045512.2_19mer_win1_00306 306 324 57 TCCAACTCAGTTTGCCTGT 1260ACAGGCAAACTGAGTTGGA NC_045512.2_19mer_win1_00455 455 473 58CTTGAACAGCCCTATGTGT 1261 ACACATAGGGCTGTTCAAGNC_045512.2_19mer_win1_00456 456 474 59 TTGAACAGCCCTATGTGTT 1262AACACATAGGGCTGTTCAA NC_045512.2_19mer_win1_00457 457 475 60TGAACAGCCCTATGTGTTC 1263 GAACACATAGGGCTGTTCANC_045512.2_19mer_win1_00458 458 476 61 GAACAGCCCTATGTGTTCA 1264TGAACACATAGGGCTGTTC NC_045512.2_19mer_win1_00459 459 477 62AACAGCCCTATGTGTTCAT 1265 ATGAACACATAGGGCTGTTNC_045512.2_19mer_win1_00626 626 644 63 GTTCTTCTTCGTAAGAACG 1266CGTTCTTACGAAGAAGAAC NC_045512.2_19mer_win1_00627 627 645 64TTCTTCTTCGTAAGAACGG 1267 CCGTTCTTACGAAGAAGAANC_045512.2_19mer_win1_00628 628 646 65 TCTTCTTCGTAAGAACGGT 1268ACCGTTCTTACGAAGAAGA NC_045512.2_19mer_win1_00629 629 647 66CTTCTTCGTAAGAACGGTA 1269 TACCGTTCTTACGAAGAAGNC_045512.2_19mer_win1_00630 630 648 67 TTCTTCGTAAGAACGGTAA 1270TTACCGTTCTTACGAAGAA NC_045512.2_19mer_win1_00631 631 649 68TCTTCGTAAGAACGGTAAT 1271 ATTACCGTTCTTACGAAGANC_045512.2_19mer_win1_00632 632 650 69 CTTCGTAAGAACGGTAATA 1272TATTACCGTTCTTACGAAG NC_045512.2_19mer_win1_00633 633 651 70TTCGTAAGAACGGTAATAA 1273 TTATTACCGTTCTTACGAANC_045512.2_19mer_win1_00704 704 722 71 GACGAGCTTGGCACTGATC 1274GATCAGTGCCAAGCTCGTC NC_045512.2_19mer_win1_00705 705 723 72ACGAGCTTGGCACTGATCC 1275 GGATCAGTGCCAAGCTCGTNC_045512.2_19mer_win1_03352 3352 3370 73 TGGTTATTTAAAACTTACT 1276AGTAAGTTTTAAATAACCA NC_045512.2_19mer_win1_03353 3353 3371 74GGTTATTTAAAACTTACTG 1277 CAGTAAGTTTTAAATAACCNC_045512.2_19mer_win1_03354 3354 3372 75 GTTATTTAAAACTTACTGA 1278TCAGTAAGTTTTAAATAAC NC_045512.2_19mer_win1_03355 3355 3373 76TTATTTAAAACTTACTGAC 1279 GTCAGTAAGTTTTAAATAANC_045512.2_19mer_win1_03356 3356 3374 77 TATTTAAAACTTACTGACA 1280TGTCAGTAAGTTTTAAATA NC_045512.2_19mer_win1_03357 3357 3375 78ATTTAAAACTTACTGACAA 1281 TTGTCAGTAAGTTTTAAATNC_045512.2_19mer_win1_03358 3358 3376 79 TTTAAAACTTACTGACAAT 1282ATTGTCAGTAAGTTTTAAA NC_045512.2_19mer_win1_03359 3359 3377 80TTAAAACTTACTGACAATG 1283 CATTGTCAGTAAGTTTTAANC_045512.2_19mer_win1_03360 3360 3378 81 TAAAACTTACTGACAATGT 1284ACATTGTCAGTAAGTTTTA NC_045512.2_19mer_win1_05384 5384 5402 82GCTGCTAACTTTTGTGCAC 1285 GTGCACAAAAGTTAGCAGCNC_045512.2_19mer_win1_05385 5385 5403 83 CTGCTAACTTTTGTGCACT 1286AGTGCACAAAAGTTAGCAG NC_045512.2_19mer_win1_06406 6406 6424 84CTCTGAAGAAGTAGTGGAA 1287 TTCCACTACTTCTTCAGAGNC_045512.2_19mer_win1_06407 6407 6425 85 TCTGAAGAAGTAGTGGAAA 1288TTTCCACTACTTCTTCAGA NC_045512.2_19mer_win1_06408 6408 6426 86CTGAAGAAGTAGTGGAAAA 1289 TTTTCCACTACTTCTTCAGNC_045512.2_19mer_win1_06409 6409 6427 87 TGAAGAAGTAGTGGAAAAT 1290ATTTTCCACTACTTCTTCA NC_045512.2_19mer_win1_06410 6410 6428 88GAAGAAGTAGTGGAAAATC 1291 GATTTTCCACTACTTCTTCNC_045512.2_19mer_win1_06411 6411 6429 89 AAGAAGTAGTGGAAAATCC 1292GGATTTTCCACTACTTCTT NC_045512.2_19mer_win1_06412 6412 6430 90AGAAGTAGTGGAAAATCCT 1293 AGGATTTTCCACTACTTCTNC_045512.2_19mer_win1_06413 6413 6431 91 GAAGTAGTGGAAAATCCTA 1294TAGGATTTTCCACTACTTC NC_045512.2_19mer_win1_06414 6414 6432 92AAGTAGTGGAAAATCCTAC 1295 GTAGGATTTTCCACTACTTNC_045512.2_19mer_win1_06415 6415 6433 93 AGTAGTGGAAAATCCTACC 1296GGTAGGATTTTCCACTACT NC_045512.2_19mer_win1_06461 6461 6479 94GTGAAAACTACCGAAGTTG 1297 CAACTTCGGTAGTTTTCACNC_045512.2_19mer_win1_06462 6462 6480 95 TGAAAACTACCGAAGTTGT 1298ACAACTTCGGTAGTTTTCA NC_045512.2_19mer_win1_06463 6463 6481 96GAAAACTACCGAAGTTGTA 1299 TACAACTTCGGTAGTTTTCNC_045512.2_19mer_win1_06464 6464 6482 97 AAAACTACCGAAGTTGTAG 1300CTACAACTTCGGTAGTTTT NC_045512.2_19mer_win1_06465 6465 6483 98AAACTACCGAAGTTGTAGG 1301 CCTACAACTTCGGTAGTTTNC_045512.2_19mer_win1_07532 7532 7550 99 TGTACAACTATTGTTAATG 1302CATTAACAATAGTTGTACA NC_045512.2_19mer_win1_07533 7533 7551 100GTACAACTATTGTTAATGG 1303 CCATTAACAATAGTTGTACNC_045512.2_19mer_win1_09588 9588 9606 101 TTTACTTGTACTTGACATT 1304AATGTCAAGTACAAGTAAA NC_045512.2_19mer_win1_10484 10484 10502 102TCATGTGGTAGTGTTGGTT 1305 AACCAACACTACCACATGANC_045512.2_19mer_win1_10485 10485 10503 103 CATGTGGTAGTGTTGGTTT 1306AAACCAACACTACCACATG NC_045512.2_19mer_win1_10486 10486 10504 104ATGTGGTAGTGTTGGTTTT 1307 AAAACCAACACTACCACATNC_045512.2_19mer_win1_10487 10487 10505 105 TGTGGTAGTGTTGGTTTTA 1308TAAAACCAACACTACCACA NC_045512.2_19mer_win1_10488 10488 10506 106GTGGTAGTGTTGGTTTTAA 1309 TTAAAACCAACACTACCACNC_045512.2_19mer_win1_10489 10489 10507 107 TGGTAGTGTTGGTTTTAAC 1310GTTAAAACCAACACTACCA NC_045512.2_19mer_win1_10490 10490 10508 108GGTAGTGTTGGTTTTAACA 1311 TGTTAAAACCAACACTACCNC_045512.2_19mer_win1_10491 10491 10509 109 GTAGTGTTGGTTTTAACAT 1312ATGTTAAAACCAACACTAC NC_045512.2_19mer_win1_11609 11609 11627 110GTTTATTGTTTCTTAGGCT 1313 AGCCTAAGAAACAATAAACNC_045512.2_19mer_win1_11610 11610 11628 111 TTTATTGTTTCTTAGGCTA 1314TAGCCTAAGAAACAATAAA NC_045512.2_19mer_win1_11611 11611 11629 112TTATTGTTTCTTAGGCTAT 1315 ATAGCCTAAGAAACAATAANC_045512.2_19mer_win1_11612 11612 11630 113 TATTGTTTCTTAGGCTATT 1316AATAGCCTAAGAAACAATA NC_045512.2_19mer_win1_11834 11834 11852 114ACTGTACAGTCTAAAATGT 1317 ACATTTTAGACTGTACAGTNC_045512.2_19mer_win1_11835 11835 11853 115 CTGTACAGTCTAAAATGTC 1318GACATTTTAGACTGTACAG NC_045512.2_19mer_win1_12023 12023 12041 116TCCATGCAGGGTGCTGTAG 1319 CTACAGCACCCTGCATGGANC_045512.2_19mer_win1_12024 12024 12042 117 CCATGCAGGGTGCTGTAGA 1320TCTACAGCACCCTGCATGG NC_045512.2_19mer_win1_12025 12025 12043 118CATGCAGGGTGCTGTAGAC 1321 GTCTACAGCACCCTGCATGNC_045512.2_19mer_win1_12026 12026 12044 119 ATGCAGGGTGCTGTAGACA 1322TGTCTACAGCACCCTGCAT NC_045512.2_19mer_win1_12027 12027 12045 120TGCAGGGTGCTGTAGACAT 1323 ATGTCTACAGCACCCTGCANC_045512.2_19mer_win1_12212 12212 12230 121 TCTTTGAATGTGGCTAAAT 1324ATTTAGCCACATTCAAAGA NC_045512.2_19mer_win1_12213 12213 12231 122CTTTGAATGTGGCTAAATC 1325 GATTTAGCCACATTCAAAGNC_045512.2_19mer_win1_12214 12214 12232 123 TTTGAATGTGGCTAAATCT 1326AGATTTAGCCACATTCAAA NC_045512.2_19mer_win1_12215 12215 12233 124TTGAATGTGGCTAAATCTG 1327 CAGATTTAGCCACATTCAANC_045512.2_19mer_win1_12216 12216 12234 125 TGAATGTGGCTAAATCTGA 1328TCAGATTTAGCCACATTCA NC_045512.2_19mer_win1_12401 12401 12419 126AACAACATTATCAACAATG 1329 CATTGTTGATAATGTTGTTNC_045512.2_19mer_win1_12402 12402 12420 127 ACAACATTATCAACAATGC 1330GCATTGTTGATAATGTTGT NC_045512.2_19mer_win1_12839 12839 12857 128AAATGGGCTAGATTCCCTA 1331 TAGGGAATCTAGCCCATTTNC_045512.2_19mer_win1_12840 12840 12858 129 AATGGGCTAGATTCCCTAA 1332TTAGGGAATCTAGCCCATT NC_045512.2_19mer_win1_12841 12841 12859 130ATGGGCTAGATTCCCTAAG 1333 CTTAGGGAATCTAGCCCATNC_045512.2_19mer_win1_12842 12842 12860 131 TGGGCTAGATTCCCTAAGA 1334TCTTAGGGAATCTAGCCCA NC_045512.2_19mer_win1_12843 12843 12861 132GGGCTAGATTCCCTAAGAG 1335 CTCTTAGGGAATCTAGCCCNC_045512.2_19mer_win1_12844 12844 12862 133 GGCTAGATTCCCTAAGAGT 1336ACTCTTAGGGAATCTAGCC NC_045512.2_19mer_win1_12845 12845 12863 134GCTAGATTCCCTAAGAGTG 1337 CACTCTTAGGGAATCTAGCNC_045512.2_19mer_win1_12846 12846 12864 135 CTAGATTCCCTAAGAGTGA 1338TCACTCTTAGGGAATCTAG NC_045512.2_19mer_win1_12847 12847 12865 136TAGATTCCCTAAGAGTGAT 1339 ATCACTCTTAGGGAATCTANC_045512.2_19mer_win1_12848 12848 12866 137 AGATTCCCTAAGAGTGATG 1340CATCACTCTTAGGGAATCT NC_045512.2_19mer_win1_12849 12849 12867 138GATTCCCTAAGAGTGATGG 1341 CCATCACTCTTAGGGAATCNC_045512.2_19mer_win1_12885 12885 12903 139 CAGAACTGGAACCACCTTG 1342CAAGGTGGTTCCAGTTCTG NC_045512.2_19mer_win1_12886 12886 12904 140AGAACTGGAACCACCTTGT 1343 ACAAGGTGGTTCCAGTTCTNC_045512.2_19mer_win1_12887 12887 12905 141 GAACTGGAACCACCTTGTA 1344TACAAGGTGGTTCCAGTTC NC_045512.2_19mer_win1_12888 12888 12906 142AACTGGAACCACCTTGTAG 1345 CTACAAGGTGGTTCCAGTTNC_045512.2_19mer_win1_12889 12889 12907 143 ACTGGAACCACCTTGTAGG 1346CCTACAAGGTGGTTCCAGT NC_045512.2_19mer_win1_12890 12890 12908 144CTGGAACCACCTTGTAGGT 1347 ACCTACAAGGTGGTTCCAGNC_045512.2_19mer_win1_12891 12891 12909 145 TGGAACCACCTTGTAGGTT 1348AACCTACAAGGTGGTTCCA NC_045512.2_19mer_win1_12892 12892 12910 146GGAACCACCTTGTAGGTTT 1349 AAACCTACAAGGTGGTTCCNC_045512.2_19mer_win1_12893 12893 12911 147 GAACCACCTTGTAGGTTTG 1350CAAACCTACAAGGTGGTTC NC_045512.2_19mer_win1_12894 12894 12912 148AACCACCTTGTAGGTTTGT 1351 ACAAACCTACAAGGTGGTTNC_045512.2_19mer_win1_12895 12895 12913 149 ACCACCTTGTAGGTTTGTT 1352AACAAACCTACAAGGTGGT NC_045512.2_19mer_win1_12896 12896 12914 150CCACCTTGTAGGTTTGTTA 1353 TAACAAACCTACAAGGTGGNC_045512.2_19mer_win1_12897 12897 12915 151 CACCTTGTAGGTTTGTTAC 1354GTAACAAACCTACAAGGTG NC_045512.2_19mer_win1_12898 12898 12916 152ACCTTGTAGGTTTGTTACA 1355 TGTAACAAACCTACAAGGTNC_045512.2_19mer_win1_12899 12899 12917 153 CCTTGTAGGTTTGTTACAG 1356CTGTAACAAACCTACAAGG NC_045512.2_19mer_win1_12900 12900 12918 154CTTGTAGGTTTGTTACAGA 1357 TCTGTAACAAACCTACAAGNC_045512.2_19mer_win1_12901 12901 12919 155 TTGTAGGTTTGTTACAGAC 1358GTCTGTAACAAACCTACAA NC_045512.2_19mer_win1_12902 12902 12920 156TGTAGGTTTGTTACAGACA 1359 TGTCTGTAACAAACCTACANC_045512.2_19mer_win1_12903 12903 12921 157 GTAGGTTTGTTACAGACAC 1360GTGTCTGTAACAAACCTAC NC_045512.2_19mer_win1_12904 12904 12922 158TAGGTTTGTTACAGACACA 1361 TGTGTCTGTAACAAACCTANC_045512.2_19mer_win1_12905 12905 12923 159 AGGTTTGTTACAGACACAC 1362GTGTGTCTGTAACAAACCT NC_045512.2_19mer_win1_12906 12906 12924 160GGTTTGTTACAGACACACC 1363 GGTGTGTCTGTAACAAACCNC_045512.2_19mer_win1_12966 12966 12984 161 TAAACAACCTAAATAGAGG 1364CCTCTATTTAGGTTGTTTA NC_045512.2_19mer_win1_12967 12967 12985 162AAACAACCTAAATAGAGGT 1365 ACCTCTATTTAGGTTGTTTNC_045512.2_19mer_win1_12968 12968 12986 163 AACAACCTAAATAGAGGTA 1366TACCTCTATTTAGGTTGTT NC_045512.2_19mer_win1_12969 12969 12987 164ACAACCTAAATAGAGGTAT 1367 ATACCTCTATTTAGGTTGTNC_045512.2_19mer_win1_12970 12970 12988 165 CAACCTAAATAGAGGTATG 1368CATACCTCTATTTAGGTTG NC_045512.2_19mer_win1_12971 12971 12989 166AACCTAAATAGAGGTATGG 1369 CCATACCTCTATTTAGGTTNC_045512.2_19mer_win1_12972 12972 12990 167 ACCTAAATAGAGGTATGGT 1370ACCATACCTCTATTTAGGT NC_045512.2_19mer_win1_13151 13151 13169 168AAGATGTTGTGTACACACA 1371 TGTGTGTACACAACATCTTNC_045512.2_19mer_win1_13152 13152 13170 169 AGATGTTGTGTACACACAC 1372GTGTGTGTACACAACATCT NC_045512.2_19mer_win1_13153 13153 13171 170GATGTTGTGTACACACACT 1373 AGTGTGTGTACACAACATCNC_045512.2_19mer_win1_13154 13154 13172 171 ATGTTGTGTACACACACTG 1374CAGTGTGTGTACACAACAT NC_045512.2_19mer_win1_13155 13155 13173 172TGTTGTGTACACACACTGG 1375 CCAGTGTGTGTACACAACANC_045512.2_19mer_win1_13156 13156 13174 173 GTTGTGTACACACACTGGT 1376ACCAGTGTGTGTACACAAC NC_045512.2_19mer_win1_13157 13157 13175 174TTGTGTACACACACTGGTA 1377 TACCAGTGTGTGTACACAANC_045512.2_19mer_win1_13158 13158 13176 175 TGTGTACACACACTGGTAC 1378GTACCAGTGTGTGTACACA NC_045512.2_19mer_win1_13363 13363 13381 176AAACACAGTCTGTACCGTC 1379 GACGGTACAGACTGTGTTTNC_045512.2_19mer_win1_13364 13364 13382 177 AACACAGTCTGTACCGTCT 1380AGACGGTACAGACTGTGTT NC_045512.2_19mer_win1_13365 13365 13383 178ACACAGTCTGTACCGTCTG 1381 CAGACGGTACAGACTGTGTNC_045512.2_19mer_win1_13366 13366 13384 179 CACAGTCTGTACCGTCTGC 1382GCAGACGGTACAGACTGTG NC_045512.2_19mer_win1_13367 13367 13385 180ACAGTCTGTACCGTCTGCG 1383 CGCAGACGGTACAGACTGTNC_045512.2_19mer_win1_13368 13368 13386 181 CAGTCTGTACCGTCTGCGG 1384CCGCAGACGGTACAGACTG NC_045512.2_19mer_win1_13388 13388 13406 182ATGTGGAAAGGTTATGGCT 1385 AGCCATAACCTTTCCACATNC_045512.2_19mer_win1_13389 13389 13407 183 TGTGGAAAGGTTATGGCTG 1386CAGCCATAACCTTTCCACA NC_045512.2_19mer_win1_13390 13390 13408 184GTGGAAAGGTTATGGCTGT 1387 ACAGCCATAACCTTTCCACNC_045512.2_19mer_win1_13391 13391 13409 185 TGGAAAGGTTATGGCTGTA 1388TACAGCCATAACCTTTCCA NC_045512.2_19mer_win1_13392 13392 13410 186GGAAAGGTTATGGCTGTAG 1389 CTACAGCCATAACCTTTCCNC_045512.2_19mer_win1_13393 13393 13411 187 GAAAGGTTATGGCTGTAGT 1390ACTACAGCCATAACCTTTC NC_045512.2_19mer_win1_13394 13394 13412 188AAAGGTTATGGCTGTAGTT 1391 AACTACAGCCATAACCTTTNC_045512.2_19mer_win1_13395 13395 13413 189 AAGGTTATGGCTGTAGTTG 1392CAACTACAGCCATAACCTT NC_045512.2_19mer_win1_13396 13396 13414 190AGGTTATGGCTGTAGTTGT 1393 ACAACTACAGCCATAACCTNC_045512.2_19mer_win1_13397 13397 13415 191 GGTTATGGCTGTAGTTGTG 1394CACAACTACAGCCATAACC NC_045512.2_19mer_win1_13398 13398 13416 192GTTATGGCTGTAGTTGTGA 1395 TCACAACTACAGCCATAACNC_045512.2_19mer_win1_13458 13458 13476 193 CGTTTTTAAACGGGTTTGC 1396GCAAACCCGTTTAAAAACG NC_045512.2_19mer_win1_13459 13459 13477 194GTTTTTAAACGGGTTTGCG 1397 CGCAAACCCGTTTAAAAACNC_045512.2_19mer_win1_13460 13460 13478 195 TTTTTAAACGGGTTTGCGG 1398CCGCAAACCCGTTTAAAAA NC_045512.2_19mer_win1_13461 13461 13479 196TTTTAAACGGGTTTGCGGT 1399 ACCGCAAACCCGTTTAAAANC_045512.2_19mer_win1_13462 13462 13480 197 TTTAAACGGGTTTGCGGTG 1400CACCGCAAACCCGTTTAAA NC_045512.2_19mer_win1_13463 13463 13481 198TTAAACGGGTTTGCGGTGT 1401 ACACCGCAAACCCGTTTAANC_045512.2_19mer_win1_13464 13464 13482 199 TAAACGGGTTTGCGGTGTA 1402TACACCGCAAACCCGTTTA NC_045512.2_19mer_win1_13465 13465 13483 200AAACGGGTTTGCGGTGTAA 1403 TTACACCGCAAACCCGTTTNC_045512.2_19mer_win1_13466 13466 13484 201 AACGGGTTTGCGGTGTAAG 1404CTTACACCGCAAACCCGTT NC_045512.2_19mer_win1_13467 13467 13485 202ACGGGTTTGCGGTGTAAGT 1405 ACTTACACCGCAAACCCGTNC_045512.2_19mer_win1_13468 13468 13486 203 CGGGTTTGCGGTGTAAGTG 1406CACTTACACCGCAAACCCG NC_045512.2_19mer_win1_13469 13469 13487 204GGGTTTGCGGTGTAAGTGC 1407 GCACTTACACCGCAAACCCNC_045512.2_19mer_win1_13470 13470 13488 205 GGTTTGCGGTGTAAGTGCA 1408TGCACTTACACCGCAAACC NC_045512.2_19mer_win1_13471 13471 13489 206GTTTGCGGTGTAAGTGCAG 1409 CTGCACTTACACCGCAAACNC_045512.2_19mer_win1_13472 13472 13490 207 TTTGCGGTGTAAGTGCAGC 1410GCTGCACTTACACCGCAAA NC_045512.2_19mer_win1_13473 13473 13491 208TTGCGGTGTAAGTGCAGCC 1411 GGCTGCACTTACACCGCAANC_045512.2_19mer_win1_13474 13474 13492 209 TGCGGTGTAAGTGCAGCCC 1412GGGCTGCACTTACACCGCA NC_045512.2_19mer_win1_13475 13475 13493 210GCGGTGTAAGTGCAGCCCG 1413 CGGGCTGCACTTACACCGCNC_045512.2_19mer_win1_13476 13476 13494 211 CGGTGTAAGTGCAGCCCGT 1414ACGGGCTGCACTTACACCG NC_045512.2_19mer_win1_13477 13477 13495 212GGTGTAAGTGCAGCCCGTC 1415 GACGGGCTGCACTTACACCNC_045512.2_19mer_win1_13478 13478 13496 213 GTGTAAGTGCAGCCCGTCT 1416AGACGGGCTGCACTTACAC NC_045512.2_19mer_win1_13479 13479 13497 214TGTAAGTGCAGCCCGTCTT 1417 AAGACGGGCTGCACTTACANC_045512.2_19mer_win1_13480 13480 13498 215 GTAAGTGCAGCCCGTCTTA 1418TAAGACGGGCTGCACTTAC NC_045512.2_19mer_win1_13481 13481 13499 216TAAGTGCAGCCCGTCTTAC 1419 GTAAGACGGGCTGCACTTANC_045512.2_19mer_win1_13482 13482 13500 217 AAGTGCAGCCCGTCTTACA 1420TGTAAGACGGGCTGCACTT NC_045512.2_19mer_win1_13483 13483 13501 218AGTGCAGCCCGTCTTACAC 1421 GTGTAAGACGGGCTGCACTNC_045512.2_19mer_win1_13484 13484 13502 219 GTGCAGCCCGTCTTACACC 1422GGTGTAAGACGGGCTGCAC NC_045512.2_19mer_win1_13485 13485 13503 220TGCAGCCCGTCTTACACCG 1423 CGGTGTAAGACGGGCTGCANC_045512.2_19mer_win1_13486 13486 13504 221 GCAGCCCGTCTTACACCGT 1424ACGGTGTAAGACGGGCTGC NC_045512.2_19mer_win1_13487 13487 13505 222CAGCCCGTCTTACACCGTG 1425 CACGGTGTAAGACGGGCTGNC_045512.2_19mer_win1_13488 13488 13506 223 AGCCCGTCTTACACCGTGC 1426GCACGGTGTAAGACGGGCT NC_045512.2_19mer_win1_13489 13489 13507 224GCCCGTCTTACACCGTGCG 1427 CGCACGGTGTAAGACGGGCNC_045512.2_19mer_win1_13490 13490 13508 225 CCCGTCTTACACCGTGCGG 1428CCGCACGGTGTAAGACGGG NC_045512.2_19mer_win1_13491 13491 13509 226CCGTCTTACACCGTGCGGC 1429 GCCGCACGGTGTAAGACGGNC_045512.2_19mer_win1_13492 13492 13510 227 CGTCTTACACCGTGCGGCA 1430TGCCGCACGGTGTAAGACG NC_045512.2_19mer_win1_13493 13493 13511 228GTCTTACACCGTGCGGCAC 1431 GTGCCGCACGGTGTAAGACNC_045512.2_19mer_win1_13494 13494 13512 229 TCTTACACCGTGCGGCACA 1432TGTGCCGCACGGTGTAAGA NC_045512.2_19mer_win1_13495 13495 13513 230CTTACACCGTGCGGCACAG 1433 CTGTGCCGCACGGTGTAAGNC_045512.2_19mer_win1_13496 13496 13514 231 TTACACCGTGCGGCACAGG 1434CCTGTGCCGCACGGTGTAA NC_045512.2_19mer_win1_13497 13497 13515 232TACACCGTGCGGCACAGGC 1435 GCCTGTGCCGCACGGTGTANC_045512.2_19mer_win1_13498 13498 13516 233 ACACCGTGCGGCACAGGCA 1436TGCCTGTGCCGCACGGTGT NC_045512.2_19mer_win1_13499 13499 13517 234CACCGTGCGGCACAGGCAC 1437 GTGCCTGTGCCGCACGGTGNC_045512.2_19mer_win1_13500 13500 13518 235 ACCGTGCGGCACAGGCACT 1438AGTGCCTGTGCCGCACGGT NC_045512.2_19mer_win1_13501 13501 13519 236CCGTGCGGCACAGGCACTA 1439 TAGTGCCTGTGCCGCACGGNC_045512.2_19mer_win1_13502 13502 13520 237 CGTGCGGCACAGGCACTAG 1440CTAGTGCCTGTGCCGCACG NC_045512.2_19mer_win1_13762 13762 13780 238GGTGACATGGTACCACATA 1441 TATGTGGTACCATGTCACCNC_045512.2_19mer_win1_13763 13763 13781 239 GTGACATGGTACCACATAT 1442ATATGTGGTACCATGTCAC NC_045512.2_19mer_win1_13764 13764 13782 240TGACATGGTACCACATATA 1443 TATATGTGGTACCATGTCANC_045512.2_19mer_win1_13765 13765 13783 241 GACATGGTACCACATATAT 1444ATATATGTGGTACCATGTC NC_045512.2_19mer_win1_13766 13766 13784 242ACATGGTACCACATATATC 1445 GATATATGTGGTACCATGTNC_045512.2_19mer_win1_13767 13767 13785 243 CATGGTACCACATATATCA 1446TGATATATGTGGTACCATG NC_045512.2_19mer_win1_13768 13768 13786 244ATGGTACCACATATATCAC 1447 GTGATATATGTGGTACCATNC_045512.2_19mer_win1_13769 13769 13787 245 TGGTACCACATATATCACG 1448CGTGATATATGTGGTACCA NC_045512.2_19mer_win1_13770 13770 13788 246GGTACCACATATATCACGT 1449 ACGTGATATATGTGGTACCNC_045512.2_19mer_win1_13771 13771 13789 247 GTACCACATATATCACGTC 1450GACGTGATATATGTGGTAC NC_045512.2_19mer_win1_13772 13772 13790 248TACCACATATATCACGTCA 1451 TGACGTGATATATGTGGTANC_045512.2_19mer_win1_14290 14290 14308 249 GACCGTTATTTTAAATATT 1452AATATTTAAAATAACGGTC NC_045512.2_19mer_win1_14291 14291 14309 250ACCGTTATTTTAAATATTG 1453 CAATATTTAAAATAACGGTNC_045512.2_19mer_win1_14292 14292 14310 251 CCGTTATTTTAAATATTGG 1454CCAATATTTAAAATAACGG NC_045512.2_19mer_win1_14293 14293 14311 252CGTTATTTTAAATATTGGG 1455 CCCAATATTTAAAATAACGNC_045512.2_19mer_win1_14294 14294 14312 253 GTTATTTTAAATATTGGGA 1456TCCCAATATTTAAAATAAC NC_045512.2_19mer_win1_14404 14404 14422 254CCACCTACAAGTTTTGGAC 1457 GTCCAAAACTTGTAGGTGGNC_045512.2_19mer_win1_14405 14405 14423 255 CACCTACAAGTTTTGGACC 1458GGTCCAAAACTTGTAGGTG NC_045512.2_19mer_win1_14406 14406 14424 256ACCTACAAGTTTTGGACCA 1459 TGGTCCAAAACTTGTAGGTNC_045512.2_19mer_win1_14407 14407 14425 257 CCTACAAGTTTTGGACCAC 1460GTGGTCCAAAACTTGTAGG NC_045512.2_19mer_win1_14408 14408 14426 258CTACAAGTTTTGGACCACT 1461 AGTGGTCCAAAACTTGTAGNC_045512.2_19mer_win1_14409 14409 14427 259 TACAAGTTTTGGACCACTA 1462TAGTGGTCCAAAACTTGTA NC_045512.2_19mer_win1_14410 14410 14428 260ACAAGTTTTGGACCACTAG 1463 CTAGTGGTCCAAAACTTGTNC_045512.2_19mer_win1_14411 14411 14429 261 CAAGTTTTGGACCACTAGT 1464ACTAGTGGTCCAAAACTTG NC_045512.2_19mer_win1_14500 14500 14518 262GTACATAATCAGGATGTAA 1465 TTACATCCTGATTATGTACNC_045512.2_19mer_win1_14501 14501 14519 263 TACATAATCAGGATGTAAA 1466TTTACATCCTGATTATGTA NC_045512.2_19mer_win1_14502 14502 14520 264ACATAATCAGGATGTAAAC 1467 GTTTACATCCTGATTATGTNC_045512.2_19mer_win1_14503 14503 14521 265 CATAATCAGGATGTAAACT 1468AGTTTACATCCTGATTATG NC_045512.2_19mer_win1_14504 14504 14522 266ATAATCAGGATGTAAACTT 1469 AAGTTTACATCCTGATTATNC_045512.2_19mer_win1_14505 14505 14523 267 TAATCAGGATGTAAACTTA 1470TAAGTTTACATCCTGATTA NC_045512.2_19mer_win1_14506 14506 14524 268AATCAGGATGTAAACTTAC 1471 GTAAGTTTACATCCTGATTNC_045512.2_19mer_win1_14507 14507 14525 269 ATCAGGATGTAAACTTACA 1472TGTAAGTTTACATCCTGAT NC_045512.2_19mer_win1_14508 14508 14526 270TCAGGATGTAAACTTACAT 1473 ATGTAAGTTTACATCCTGANC_045512.2_19mer_win1_14509 14509 14527 271 CAGGATGTAAACTTACATA 1474TATGTAAGTTTACATCCTG NC_045512.2_19mer_win1_14510 14510 14528 272AGGATGTAAACTTACATAG 1475 CTATGTAAGTTTACATCCTNC_045512.2_19mer_win1_14511 14511 14529 273 GGATGTAAACTTACATAGC 1476GCTATGTAAGTTTACATCC NC_045512.2_19mer_win1_14512 14512 14530 274GATGTAAACTTACATAGCT 1477 AGCTATGTAAGTTTACATCNC_045512.2_19mer_win1_14513 14513 14531 275 ATGTAAACTTACATAGCTC 1478GAGCTATGTAAGTTTACAT NC_045512.2_19mer_win1_14623 14623 14641 276TGCTTTTCAGTAGCTGCAC 1479 GTGCAGCTACTGAAAAGCANC_045512.2_19mer_win1_14624 14624 14642 277 GCTTTTCAGTAGCTGCACT 1480AGTGCAGCTACTGAAAAGC NC_045512.2_19mer_win1_14650 14650 14668 278AATGTTGCTTTTCAAACTG 1481 CAGTTTGAAAAGCAACATTNC_045512.2_19mer_win1_14651 14651 14669 279 ATGTTGCTTTTCAAACTGT 1482ACAGTTTGAAAAGCAACAT NC_045512.2_19mer_win1_14652 14652 14670 280TGTTGCTTTTCAAACTGTC 1483 GACAGTTTGAAAAGCAACANC_045512.2_19mer_win1_14653 14653 14671 281 GTTGCTTTTCAAACTGTCA 1484TGACAGTTTGAAAAGCAAC NC_045512.2_19mer_win1_14654 14654 14672 282TTGCTTTTCAAACTGTCAA 1485 TTGACAGTTTGAAAAGCAANC_045512.2_19mer_win1_14655 14655 14673 283 TGCTTTTCAAACTGTCAAA 1486TTTGACAGTTTGAAAAGCA NC_045512.2_19mer_win1_14656 14656 14674 284GCTTTTCAAACTGTCAAAC 1487 GTTTGACAGTTTGAAAAGCNC_045512.2_19mer_win1_14657 14657 14675 285 CTTTTCAAACTGTCAAACC 1488GGTTTGACAGTTTGAAAAG NC_045512.2_19mer_win1_14658 14658 14676 286TTTTCAAACTGTCAAACCC 1489 GGGTTTGACAGTTTGAAAANC_045512.2_19mer_win1_14659 14659 14677 287 TTTCAAACTGTCAAACCCG 1490CGGGTTTGACAGTTTGAAA NC_045512.2_19mer_win1_14660 14660 14678 288TTCAAACTGTCAAACCCGG 1491 CCGGGTTTGACAGTTTGAANC_045512.2_19mer_win1_14661 14661 14679 289 TCAAACTGTCAAACCCGGT 1492ACCGGGTTTGACAGTTTGA NC_045512.2_19mer_win1_14662 14662 14680 290CAAACTGTCAAACCCGGTA 1493 TACCGGGTTTGACAGTTTGNC_045512.2_19mer_win1_14663 14663 14681 291 AAACTGTCAAACCCGGTAA 1494TTACCGGGTTTGACAGTTT NC_045512.2_19mer_win1_14664 14664 14682 292AACTGTCAAACCCGGTAAT 1495 ATTACCGGGTTTGACAGTTNC_045512.2_19mer_win1_14665 14665 14683 293 ACTGTCAAACCCGGTAATT 1496AATTACCGGGTTTGACAGT NC_045512.2_19mer_win1_14666 14666 14684 294CTGTCAAACCCGGTAATTT 1497 AAATTACCGGGTTTGACAGNC_045512.2_19mer_win1_14667 14667 14685 295 TGTCAAACCCGGTAATTTT 1498AAAATTACCGGGTTTGACA NC_045512.2_19mer_win1_14668 14668 14686 296GTCAAACCCGGTAATTTTA 1499 TAAAATTACCGGGTTTGACNC_045512.2_19mer_win1_14669 14669 14687 297 TCAAACCCGGTAATTTTAA 1500TTAAAATTACCGGGTTTGA NC_045512.2_19mer_win1_14698 14698 14716 298TATGACTTTGCTGTGTCTA 1501 TAGACACAGCAAAGTCATANC_045512.2_19mer_win1_14699 14699 14717 299 ATGACTTTGCTGTGTCTAA 1502TTAGACACAGCAAAGTCAT NC_045512.2_19mer_win1_14722 14722 14740 300TTCTTTAAGGAAGGAAGTT 1503 AACTTCCTTCCTTAAAGAANC_045512.2_19mer_win1_14723 14723 14741 301 TCTTTAAGGAAGGAAGTTC 1504GAACTTCCTTCCTTAAAGA NC_045512.2_19mer_win1_14724 14724 14742 302CTTTAAGGAAGGAAGTTCT 1505 AGAACTTCCTTCCTTAAAGNC_045512.2_19mer_win1_14725 14725 14743 303 TTTAAGGAAGGAAGTTCTG 1506CAGAACTTCCTTCCTTAAA NC_045512.2_19mer_win1_14726 14726 14744 304TTAAGGAAGGAAGTTCTGT 1507 ACAGAACTTCCTTCCTTAANC_045512.2_19mer_win1_14727 14727 14745 305 TAAGGAAGGAAGTTCTGTT 1508AACAGAACTTCCTTCCTTA NC_045512.2_19mer_win1_14728 14728 14746 306AAGGAAGGAAGTTCTGTTG 1509 CAACAGAACTTCCTTCCTTNC_045512.2_19mer_win1_14729 14729 14747 307 AGGAAGGAAGTTCTGTTGA 1510TCAACAGAACTTCCTTCCT NC_045512.2_19mer_win1_14730 14730 14748 308GGAAGGAAGTTCTGTTGAA 1511 TTCAACAGAACTTCCTTCCNC_045512.2_19mer_win1_14750 14750 14768 309 TAAAACACTTCTTCTTTGC 1512GCAAAGAAGAAGTGTTTTA NC_045512.2_19mer_win1_14751 14751 14769 310AAAACACTTCTTCTTTGCT 1513 AGCAAAGAAGAAGTGTTTTNC_045512.2_19mer_win1_14752 14752 14770 311 AAACACTTCTTCTTTGCTC 1514GAGCAAAGAAGAAGTGTTT NC_045512.2_19mer_win1_14753 14753 14771 312AACACTTCTTCTTTGCTCA 1515 TGAGCAAAGAAGAAGTGTTNC_045512.2_19mer_win1_14754 14754 14772 313 ACACTTCTTCTTTGCTCAG 1516CTGAGCAAAGAAGAAGTGT NC_045512.2_19mer_win1_14755 14755 14773 314CACTTCTTCTTTGCTCAGG 1517 CCTGAGCAAAGAAGAAGTGNC_045512.2_19mer_win1_14756 14756 14774 315 ACTTCTTCTTTGCTCAGGA 1518TCCTGAGCAAAGAAGAAGT NC_045512.2_19mer_win1_14757 14757 14775 316CTTCTTCTTTGCTCAGGAT 1519 ATCCTGAGCAAAGAAGAAGNC_045512.2_19mer_win1_14758 14758 14776 317 TTCTTCTTTGCTCAGGATG 1520CATCCTGAGCAAAGAAGAA NC_045512.2_19mer_win1_14759 14759 14777 318TCTTCTTTGCTCAGGATGG 1521 CCATCCTGAGCAAAGAAGANC_045512.2_19mer_win1_14821 14821 14839 319 CCAACAATGTGTGATATCA 1522TGATATCACACATTGTTGG NC_045512.2_19mer_win1_14822 14822 14840 320CAACAATGTGTGATATCAG 1523 CTGATATCACACATTGTTGNC_045512.2_19mer_win1_14823 14823 14841 321 AACAATGTGTGATATCAGA 1524TCTGATATCACACATTGTT NC_045512.2_19mer_win1_14824 14824 14842 322ACAATGTGTGATATCAGAC 1525 GTCTGATATCACACATTGTNC_045512.2_19mer_win1_14825 14825 14843 323 CAATGTGTGATATCAGACA 1526TGTCTGATATCACACATTG NC_045512.2_19mer_win1_14826 14826 14844 324AATGTGTGATATCAGACAA 1527 TTGTCTGATATCACACATTNC_045512.2_19mer_win1_14827 14827 14845 325 ATGTGTGATATCAGACAAC 1528GTTGTCTGATATCACACAT NC_045512.2_19mer_win1_14828 14828 14846 326TGTGTGATATCAGACAACT 1529 AGTTGTCTGATATCACACANC_045512.2_19mer_win1_14854 14854 14872 327 GTAGTTGAAGTTGTTGATA 1530TATCAACAACTTCAACTAC NC_045512.2_19mer_win1_14855 14855 14873 328TAGTTGAAGTTGTTGATAA 1531 TTATCAACAACTTCAACTANC_045512.2_19mer_win1_14875 14875 14893 329 TACTTTGATTGTTACGATG 1532CATCGTAACAATCAAAGTA NC_045512.2_19mer_win1_14876 14876 14894 330ACTTTGATTGTTACGATGG 1533 CCATCGTAACAATCAAAGTNC_045512.2_19mer_win1_14877 14877 14895 331 CTTTGATTGTTACGATGGT 1534ACCATCGTAACAATCAAAG NC_045512.2_19mer_win1_14878 14878 14896 332TTTGATTGTTACGATGGTG 1535 CACCATCGTAACAATCAAANC_045512.2_19mer_win1_14879 14879 14897 333 TTGATTGTTACGATGGTGG 1536CCACCATCGTAACAATCAA NC_045512.2_19mer_win1_14880 14880 14898 334TGATTGTTACGATGGTGGC 1537 GCCACCATCGTAACAATCANC_045512.2_19mer_win1_14881 14881 14899 335 GATTGTTACGATGGTGGCT 1538AGCCACCATCGTAACAATC NC_045512.2_19mer_win1_14882 14882 14900 336ATTGTTACGATGGTGGCTG 1539 CAGCCACCATCGTAACAATNC_045512.2_19mer_win1_14883 14883 14901 337 TTGTTACGATGGTGGCTGT 1540ACAGCCACCATCGTAACAA NC_045512.2_19mer_win1_14884 14884 14902 338TGTTACGATGGTGGCTGTA 1541 TACAGCCACCATCGTAACANC_045512.2_19mer_win1_14885 14885 14903 339 GTTACGATGGTGGCTGTAT 1542ATACAGCCACCATCGTAAC NC_045512.2_19mer_win1_14962 14962 14980 340AAATGGGGTAAGGCTAGAC 1543 GTCTAGCCTTACCCCATTTNC_045512.2_19mer_win1_14963 14963 14981 341 AATGGGGTAAGGCTAGACT 1544AGTCTAGCCTTACCCCATT NC_045512.2_19mer_win1_14964 14964 14982 342ATGGGGTAAGGCTAGACTT 1545 AAGTCTAGCCTTACCCCATNC_045512.2_19mer_win1_14965 14965 14983 343 TGGGGTAAGGCTAGACTTT 1546AAAGTCTAGCCTTACCCCA NC_045512.2_19mer_win1_14966 14966 14984 344GGGGTAAGGCTAGACTTTA 1547 TAAAGTCTAGCCTTACCCCNC_045512.2_19mer_win1_14967 14967 14985 345 GGGTAAGGCTAGACTTTAT 1548ATAAAGTCTAGCCTTACCC NC_045512.2_19mer_win1_14968 14968 14986 346GGTAAGGCTAGACTTTATT 1549 AATAAAGTCTAGCCTTACCNC_045512.2_19mer_win1_14969 14969 14987 347 GTAAGGCTAGACTTTATTA 1550TAATAAAGTCTAGCCTTAC NC_045512.2_19mer_win1_14970 14970 14988 348TAAGGCTAGACTTTATTAT 1551 ATAATAAAGTCTAGCCTTANC_045512.2_19mer_win1_14971 14971 14989 349 AAGGCTAGACTTTATTATG 1552CATAATAAAGTCTAGCCTT NC_045512.2_19mer_win1_14972 14972 14990 350AGGCTAGACTTTATTATGA 1553 TCATAATAAAGTCTAGCCTNC_045512.2_19mer_win1_14992 14992 15010 351 TCAATGAGTTATGAGGATC 1554GATCCTCATAACTCATTGA NC_045512.2_19mer_win1_14993 14993 15011 352CAATGAGTTATGAGGATCA 1555 TGATCCTCATAACTCATTGNC_045512.2_19mer_win1_14994 14994 15012 353 AATGAGTTATGAGGATCAA 1556TTGATCCTCATAACTCATT NC_045512.2_19mer_win1_14995 14995 15013 354ATGAGTTATGAGGATCAAG 1557 CTTGATCCTCATAACTCATNC_045512.2_19mer_win1_14996 14996 15014 355 TGAGTTATGAGGATCAAGA 1558TCTTGATCCTCATAACTCA NC_045512.2_19mer_win1_14997 14997 15015 356GAGTTATGAGGATCAAGAT 1559 ATCTTGATCCTCATAACTCNC_045512.2_19mer_win1_14998 14998 15016 357 AGTTATGAGGATCAAGATG 1560CATCTTGATCCTCATAACT NC_045512.2_19mer_win1_14999 14999 15017 358GTTATGAGGATCAAGATGC 1561 GCATCTTGATCCTCATAACNC_045512.2_19mer_win1_15000 15000 15018 359 TTATGAGGATCAAGATGCA 1562TGCATCTTGATCCTCATAA NC_045512.2_19mer_win1_15001 15001 15019 360TATGAGGATCAAGATGCAC 1563 GTGCATCTTGATCCTCATANC_045512.2_19mer_win1_15002 15002 15020 361 ATGAGGATCAAGATGCACT 1564AGTGCATCTTGATCCTCAT NC_045512.2_19mer_win1_15055 15055 15073 362ATAACTCAAATGAATCTTA 1565 TAAGATTCATTTGAGTTATNC_045512.2_19mer_win1_15056 15056 15074 363 TAACTCAAATGAATCTTAA 1566TTAAGATTCATTTGAGTTA NC_045512.2_19mer_win1_15057 15057 15075 364AACTCAAATGAATCTTAAG 1567 CTTAAGATTCATTTGAGTTNC_045512.2_19mer_win1_15058 15058 15076 365 ACTCAAATGAATCTTAAGT 1568ACTTAAGATTCATTTGAGT NC_045512.2_19mer_win1_15059 15059 15077 366CTCAAATGAATCTTAAGTA 1569 TACTTAAGATTCATTTGAGNC_045512.2_19mer_win1_15060 15060 15078 367 TCAAATGAATCTTAAGTAT 1570ATACTTAAGATTCATTTGA NC_045512.2_19mer_win1_15061 15061 15079 368CAAATGAATCTTAAGTATG 1571 CATACTTAAGATTCATTTGNC_045512.2_19mer_win1_15062 15062 15080 369 AAATGAATCTTAAGTATGC 1572GCATACTTAAGATTCATTT NC_045512.2_19mer_win1_15063 15063 15081 370AATGAATCTTAAGTATGCC 1573 GGCATACTTAAGATTCATTNC_045512.2_19mer_win1_15064 15064 15082 371 ATGAATCTTAAGTATGCCA 1574TGGCATACTTAAGATTCAT NC_045512.2_19mer_win1_15065 15065 15083 372TGAATCTTAAGTATGCCAT 1575 ATGGCATACTTAAGATTCANC_045512.2_19mer_win1_15066 15066 15084 373 GAATCTTAAGTATGCCATT 1576AATGGCATACTTAAGATTC NC_045512.2_19mer_win1_15067 15067 15085 374AATCTTAAGTATGCCATTA 1577 TAATGGCATACTTAAGATTNC_045512.2_19mer_win1_15068 15068 15086 375 ATCTTAAGTATGCCATTAG 1578CTAATGGCATACTTAAGAT NC_045512.2_19mer_win1_15069 15069 15087 376TCTTAAGTATGCCATTAGT 1579 ACTAATGGCATACTTAAGANC_045512.2_19mer_win1_15070 15070 15088 377 CTTAAGTATGCCATTAGTG 1580CACTAATGGCATACTTAAG NC_045512.2_19mer_win1_15071 15071 15089 378TTAAGTATGCCATTAGTGC 1581 GCACTAATGGCATACTTAANC_045512.2_19mer_win1_15072 15072 15090 379 TAAGTATGCCATTAGTGCA 1582TGCACTAATGGCATACTTA NC_045512.2_19mer_win1_15073 15073 15091 380AAGTATGCCATTAGTGCAA 1583 TTGCACTAATGGCATACTTNC_045512.2_19mer_win1_15074 15074 15092 381 AGTATGCCATTAGTGCAAA 1584TTTGCACTAATGGCATACT NC_045512.2_19mer_win1_15075 15075 15093 382GTATGCCATTAGTGCAAAG 1585 CTTTGCACTAATGGCATACNC_045512.2_19mer_win1_15076 15076 15094 383 TATGCCATTAGTGCAAAGA 1586TCTTTGCACTAATGGCATA NC_045512.2_19mer_win1_15077 15077 15095 384ATGCCATTAGTGCAAAGAA 1587 TTCTTTGCACTAATGGCATNC_045512.2_19mer_win1_15078 15078 15096 385 TGCCATTAGTGCAAAGAAT 1588ATTCTTTGCACTAATGGCA NC_045512.2_19mer_win1_15079 15079 15097 386GCCATTAGTGCAAAGAATA 1589 TATTCTTTGCACTAATGGCNC_045512.2_19mer_win1_15080 15080 15098 387 CCATTAGTGCAAAGAATAG 1590CTATTCTTTGCACTAATGG NC_045512.2_19mer_win1_15081 15081 15099 388CATTAGTGCAAAGAATAGA 1591 TCTATTCTTTGCACTAATGNC_045512.2_19mer_win1_15082 15082 15100 389 ATTAGTGCAAAGAATAGAG 1592CTCTATTCTTTGCACTAAT NC_045512.2_19mer_win1_15083 15083 15101 390TTAGTGCAAAGAATAGAGC 1593 GCTCTATTCTTTGCACTAANC_045512.2_19mer_win1_15084 15084 15102 391 TAGTGCAAAGAATAGAGCT 1594AGCTCTATTCTTTGCACTA NC_045512.2_19mer_win1_15085 15085 15103 392AGTGCAAAGAATAGAGCTC 1595 GAGCTCTATTCTTTGCACTNC_045512.2_19mer_win1_15086 15086 15104 393 GTGCAAAGAATAGAGCTCG 1596CGAGCTCTATTCTTTGCAC NC_045512.2_19mer_win1_15087 15087 15105 394TGCAAAGAATAGAGCTCGC 1597 GCGAGCTCTATTCTTTGCANC_045512.2_19mer_win1_15088 15088 15106 395 GCAAAGAATAGAGCTCGCA 1598TGCGAGCTCTATTCTTTGC NC_045512.2_19mer_win1_15089 15089 15107 396CAAAGAATAGAGCTCGCAC 1599 GTGCGAGCTCTATTCTTTGNC_045512.2_19mer_win1_15090 15090 15108 397 AAAGAATAGAGCTCGCACC 1600GGTGCGAGCTCTATTCTTT NC_045512.2_19mer_win1_15091 15091 15109 398AAGAATAGAGCTCGCACCG 1601 CGGTGCGAGCTCTATTCTTNC_045512.2_19mer_win1_15092 15092 15110 399 AGAATAGAGCTCGCACCGT 1602ACGGTGCGAGCTCTATTCT NC_045512.2_19mer_win1_15093 15093 15111 400GAATAGAGCTCGCACCGTA 1603 TACGGTGCGAGCTCTATTCNC_045512.2_19mer_win1_15094 15094 15112 401 AATAGAGCTCGCACCGTAG 1604CTACGGTGCGAGCTCTATT NC_045512.2_19mer_win1_15095 15095 15113 402ATAGAGCTCGCACCGTAGC 1605 GCTACGGTGCGAGCTCTATNC_045512.2_19mer_win1_15096 15096 15114 403 TAGAGCTCGCACCGTAGCT 1606AGCTACGGTGCGAGCTCTA NC_045512.2_19mer_win1_15097 15097 15115 404AGAGCTCGCACCGTAGCTG 1607 CAGCTACGGTGCGAGCTCTNC_045512.2_19mer_win1_15098 15098 15116 405 GAGCTCGCACCGTAGCTGG 1608CCAGCTACGGTGCGAGCTC NC_045512.2_19mer_win1_15099 15099 15117 406AGCTCGCACCGTAGCTGGT 1609 ACCAGCTACGGTGCGAGCTNC_045512.2_19mer_win1_15100 15100 15118 407 GCTCGCACCGTAGCTGGTG 1610CACCAGCTACGGTGCGAGC NC_045512.2_19mer_win1_15101 15101 15119 408CTCGCACCGTAGCTGGTGT 1611 ACACCAGCTACGGTGCGAGNC_045512.2_19mer_win1_15102 15102 15120 409 TCGCACCGTAGCTGGTGTC 1612GACACCAGCTACGGTGCGA NC_045512.2_19mer_win1_15103 15103 15121 410CGCACCGTAGCTGGTGTCT 1613 AGACACCAGCTACGGTGCGNC_045512.2_19mer_win1_15104 15104 15122 411 GCACCGTAGCTGGTGTCTC 1614GAGACACCAGCTACGGTGC NC_045512.2_19mer_win1_15105 15105 15123 412CACCGTAGCTGGTGTCTCT 1615 AGAGACACCAGCTACGGTGNC_045512.2_19mer_win1_15106 15106 15124 413 ACCGTAGCTGGTGTCTCTA 1616TAGAGACACCAGCTACGGT NC_045512.2_19mer_win1_15107 15107 15125 414CCGTAGCTGGTGTCTCTAT 1617 ATAGAGACACCAGCTACGGNC_045512.2_19mer_win1_15108 15108 15126 415 CGTAGCTGGTGTCTCTATC 1618GATAGAGACACCAGCTACG NC_045512.2_19mer_win1_15109 15109 15127 416GTAGCTGGTGTCTCTATCT 1619 AGATAGAGACACCAGCTACNC_045512.2_19mer_win1_15110 15110 15128 417 TAGCTGGTGTCTCTATCTG 1620CAGATAGAGACACCAGCTA NC_045512.2_19mer_win1_15111 15111 15129 418AGCTGGTGTCTCTATCTGT 1621 ACAGATAGAGACACCAGCTNC_045512.2_19mer_win1_15112 15112 15130 419 GCTGGTGTCTCTATCTGTA 1622TACAGATAGAGACACCAGC NC_045512.2_19mer_win1_15113 15113 15131 420CTGGTGTCTCTATCTGTAG 1623 CTACAGATAGAGACACCAGNC_045512.2_19mer_win1_15114 15114 15132 421 TGGTGTCTCTATCTGTAGT 1624ACTACAGATAGAGACACCA NC_045512.2_19mer_win1_15115 15115 15133 422GGTGTCTCTATCTGTAGTA 1625 TACTACAGATAGAGACACCNC_045512.2_19mer_win1_15116 15116 15134 423 GTGTCTCTATCTGTAGTAC 1626GTACTACAGATAGAGACAC NC_045512.2_19mer_win1_15117 15117 15135 424TGTCTCTATCTGTAGTACT 1627 AGTACTACAGATAGAGACANC_045512.2_19mer_win1_15118 15118 15136 425 GTCTCTATCTGTAGTACTA 1628TAGTACTACAGATAGAGAC NC_045512.2_19mer_win1_15119 15119 15137 426TCTCTATCTGTAGTACTAT 1629 ATAGTACTACAGATAGAGANC_045512.2_19mer_win1_15120 15120 15138 427 CTCTATCTGTAGTACTATG 1630CATAGTACTACAGATAGAG NC_045512.2_19mer_win1_15121 15121 15139 428TCTATCTGTAGTACTATGA 1631 TCATAGTACTACAGATAGANC_045512.2_19mer_win1_15122 15122 15140 429 CTATCTGTAGTACTATGAC 1632GTCATAGTACTACAGATAG NC_045512.2_19mer_win1_15172 15172 15190 430TCAATAGCCGCCACTAGAG 1633 CTCTAGTGGCGGCTATTGANC_045512.2_19mer_win1_15173 15173 15191 431 CAATAGCCGCCACTAGAGG 1634CCTCTAGTGGCGGCTATTG NC_045512.2_19mer_win1_15174 15174 15192 432AATAGCCGCCACTAGAGGA 1635 TCCTCTAGTGGCGGCTATTNC_045512.2_19mer_win1_15175 15175 15193 433 ATAGCCGCCACTAGAGGAG 1636CTCCTCTAGTGGCGGCTAT NC_045512.2_19mer_win1_15176 15176 15194 434TAGCCGCCACTAGAGGAGC 1637 GCTCCTCTAGTGGCGGCTANC_045512.2_19mer_win1_15177 15177 15195 435 AGCCGCCACTAGAGGAGCT 1638AGCTCCTCTAGTGGCGGCT NC_045512.2_19mer_win1_15178 15178 15196 436GCCGCCACTAGAGGAGCTA 1639 TAGCTCCTCTAGTGGCGGCNC_045512.2_19mer_win1_15179 15179 15197 437 CCGCCACTAGAGGAGCTAC 1640GTAGCTCCTCTAGTGGCGG NC_045512.2_19mer_win1_15180 15180 15198 438CGCCACTAGAGGAGCTACT 1641 AGTAGCTCCTCTAGTGGCGNC_045512.2_19mer_win1_15181 15181 15199 439 GCCACTAGAGGAGCTACTG 1642CAGTAGCTCCTCTAGTGGC NC_045512.2_19mer_win1_15182 15182 15200 440CCACTAGAGGAGCTACTGT 1643 ACAGTAGCTCCTCTAGTGGNC_045512.2_19mer_win1_15310 15310 15328 441 AGAGCCATGCCTAACATGC 1644GCATGTTAGGCATGGCTCT NC_045512.2_19mer_win1_15311 15311 15329 442GAGCCATGCCTAACATGCT 1645 AGCATGTTAGGCATGGCTCNC_045512.2_19mer_win1_15312 15312 15330 443 AGCCATGCCTAACATGCTT 1646AAGCATGTTAGGCATGGCT NC_045512.2_19mer_win1_15313 15313 15331 444GCCATGCCTAACATGCTTA 1647 TAAGCATGTTAGGCATGGCNC_045512.2_19mer_win1_15314 15314 15332 445 CCATGCCTAACATGCTTAG 1648CTAAGCATGTTAGGCATGG NC_045512.2_19mer_win1_15346 15346 15364 446CTTGTTCTTGCTCGCAAAC 1649 GTTTGCGAGCAAGAACAAGNC_045512.2_19mer_win1_15347 15347 15365 447 TTGTTCTTGCTCGCAAACA 1650TGTTTGCGAGCAAGAACAA NC_045512.2_19mer_win1_15348 15348 15366 448TGTTCTTGCTCGCAAACAT 1651 ATGTTTGCGAGCAAGAACANC_045512.2_19mer_win1_15349 15349 15367 449 GTTCTTGCTCGCAAACATA 1652TATGTTTGCGAGCAAGAAC NC_045512.2_19mer_win1_15496 15496 15514 450ACAACTGCTTATGCTAATA 1653 TATTAGCATAAGCAGTTGTNC_045512.2_19mer_win1_15497 15497 15515 451 CAACTGCTTATGCTAATAG 1654CTATTAGCATAAGCAGTTG NC_045512.2_19mer_win1_15498 15498 15516 452AACTGCTTATGCTAATAGT 1655 ACTATTAGCATAAGCAGTTNC_045512.2_19mer_win1_15499 15499 15517 453 ACTGCTTATGCTAATAGTG 1656CACTATTAGCATAAGCAGT NC_045512.2_19mer_win1_15500 15500 15518 454CTGCTTATGCTAATAGTGT 1657 ACACTATTAGCATAAGCAGNC_045512.2_19mer_win1_15622 15622 15640 455 TATGAGTGTCTCTATAGAA 1658TTCTATAGAGACACTCATA NC_045512.2_19mer_win1_15623 15623 15641 456ATGAGTGTCTCTATAGAAA 1659 TTTCTATAGAGACACTCATNC_045512.2_19mer_win1_15624 15624 15642 457 TGAGTGTCTCTATAGAAAT 1660ATTTCTATAGAGACACTCA NC_045512.2_19mer_win1_15625 15625 15643 458GAGTGTCTCTATAGAAATA 1661 TATTTCTATAGAGACACTCNC_045512.2_19mer_win1_15626 15626 15644 459 AGTGTCTCTATAGAAATAG 1662CTATTTCTATAGAGACACT NC_045512.2_19mer_win1_15838 15838 15856 460TGGACTGAGACTGACCTTA 1663 TAAGGTCAGTCTCAGTCCANC_045512.2_19mer_win1_15839 15839 15857 461 GGACTGAGACTGACCTTAC 1664GTAAGGTCAGTCTCAGTCC NC_045512.2_19mer_win1_15840 15840 15858 462GACTGAGACTGACCTTACT 1665 AGTAAGGTCAGTCTCAGTCNC_045512.2_19mer_win1_15841 15841 15859 463 ACTGAGACTGACCTTACTA 1666TAGTAAGGTCAGTCTCAGT NC_045512.2_19mer_win1_15842 15842 15860 464CTGAGACTGACCTTACTAA 1667 TTAGTAAGGTCAGTCTCAGNC_045512.2_19mer_win1_15843 15843 15861 465 TGAGACTGACCTTACTAAA 1668TTTAGTAAGGTCAGTCTCA NC_045512.2_19mer_win1_15844 15844 15862 466GAGACTGACCTTACTAAAG 1669 CTTTAGTAAGGTCAGTCTCNC_045512.2_19mer_win1_15845 15845 15863 467 AGACTGACCTTACTAAAGG 1670CCTTTAGTAAGGTCAGTCT NC_045512.2_19mer_win1_15846 15846 15864 468GACTGACCTTACTAAAGGA 1671 TCCTTTAGTAAGGTCAGTCNC_045512.2_19mer_win1_15847 15847 15865 469 ACTGACCTTACTAAAGGAC 1672GTCCTTTAGTAAGGTCAGT NC_045512.2_19mer_win1_15848 15848 15866 470CTGACCTTACTAAAGGACC 1673 GGTCCTTTAGTAAGGTCAGNC_045512.2_19mer_win1_15849 15849 15867 471 TGACCTTACTAAAGGACCT 1674AGGTCCTTTAGTAAGGTCA NC_045512.2_19mer_win1_15850 15850 15868 472GACCTTACTAAAGGACCTC 1675 GAGGTCCTTTAGTAAGGTCNC_045512.2_19mer_win1_15851 15851 15869 473 ACCTTACTAAAGGACCTCA 1676TGAGGTCCTTTAGTAAGGT NC_045512.2_19mer_win1_15886 15886 15904 474CATACAATGCTAGTTAAAC 1677 GTTTAACTAGCATTGTATGNC_045512.2_19mer_win1_15887 15887 15905 475 ATACAATGCTAGTTAAACA 1678TGTTTAACTAGCATTGTAT NC_045512.2_19mer_win1_15985 15985 16003 476AAAACAGATGGTACACTTA 1679 TAAGTGTACCATCTGTTTTNC_045512.2_19mer_win1_15986 15986 16004 477 AAACAGATGGTACACTTAT 1680ATAAGTGTACCATCTGTTT NC_045512.2_19mer_win1_15987 15987 16005 478AACAGATGGTACACTTATG 1681 CATAAGTGTACCATCTGTTNC_045512.2_19mer_win1_15988 15988 16006 479 ACAGATGGTACACTTATGA 1682TCATAAGTGTACCATCTGT NC_045512.2_19mer_win1_15989 15989 16007 480CAGATGGTACACTTATGAT 1683 ATCATAAGTGTACCATCTGNC_045512.2_19mer_win1_15990 15990 16008 481 AGATGGTACACTTATGATT 1684AATCATAAGTGTACCATCT NC_045512.2_19mer_win1_15991 15991 16009 482GATGGTACACTTATGATTG 1685 CAATCATAAGTGTACCATCNC_045512.2_19mer_win1_15992 15992 16010 483 ATGGTACACTTATGATTGA 1686TCAATCATAAGTGTACCAT NC_045512.2_19mer_win1_16057 16057 16075 484CCTAATCAGGAGTATGCTG 1687 CAGCATACTCCTGATTAGGNC_045512.2_19mer_win1_16058 16058 16076 485 CTAATCAGGAGTATGCTGA 1688TCAGCATACTCCTGATTAG NC_045512.2_19mer_win1_16059 16059 16077 486TAATCAGGAGTATGCTGAT 1689 ATCAGCATACTCCTGATTANC_045512.2_19mer_win1_16060 16060 16078 487 AATCAGGAGTATGCTGATG 1690CATCAGCATACTCCTGATT NC_045512.2_19mer_win1_16061 16061 16079 488ATCAGGAGTATGCTGATGT 1691 ACATCAGCATACTCCTGATNC_045512.2_19mer_win1_16186 16186 16204 489 TGGGAACCTGAGTTTTATG 1692CATAAAACTCAGGTTCCCA NC_045512.2_19mer_win1_16187 16187 16205 490GGGAACCTGAGTTTTATGA 1693 TCATAAAACTCAGGTTCCCNC_045512.2_19mer_win1_16430 16430 16448 491 TAGGAGGTATGAGCTATTA 1694TAATAGCTCATACCTCCTA NC_045512.2_19mer_win1_16822 16822 16840 492GGAGAGTACACCTTTGAAA 1695 TTTCAAAGGTGTACTCTCCNC_045512.2_19mer_win1_16823 16823 16841 493 GAGAGTACACCTTTGAAAA 1696TTTTCAAAGGTGTACTCTC NC_045512.2_19mer_win1_16824 16824 16842 494AGAGTACACCTTTGAAAAA 1697 TTTTTCAAAGGTGTACTCTNC_045512.2_19mer_win1_16825 16825 16843 495 GAGTACACCTTTGAAAAAG 1698CTTTTTCAAAGGTGTACTC NC_045512.2_19mer_win1_16826 16826 16844 496AGTACACCTTTGAAAAAGG 1699 CCTTTTTCAAAGGTGTACTNC_045512.2_19mer_win1_16827 16827 16845 497 GTACACCTTTGAAAAAGGT 1700ACCTTTTTCAAAGGTGTAC NC_045512.2_19mer_win1_16828 16828 16846 498TACACCTTTGAAAAAGGTG 1701 CACCTTTTTCAAAGGTGTANC_045512.2_19mer_win1_16829 16829 16847 499 ACACCTTTGAAAAAGGTGA 1702TCACCTTTTTCAAAGGTGT NC_045512.2_19mer_win1_16830 16830 16848 500CACCTTTGAAAAAGGTGAC 1703 GTCACCTTTTTCAAAGGTGNC_045512.2_19mer_win1_16831 16831 16849 501 ACCTTTGAAAAAGGTGACT 1704AGTCACCTTTTTCAAAGGT NC_045512.2_19mer_win1_16832 16832 16850 502CCTTTGAAAAAGGTGACTA 1705 TAGTCACCTTTTTCAAAGGNC_045512.2_19mer_win1_16833 16833 16851 503 CTTTGAAAAAGGTGACTAT 1706ATAGTCACCTTTTTCAAAG NC_045512.2_19mer_win1_16834 16834 16852 504TTTGAAAAAGGTGACTATG 1707 CATAGTCACCTTTTTCAAANC_045512.2_19mer_win1_16835 16835 16853 505 TTGAAAAAGGTGACTATGG 1708CCATAGTCACCTTTTTCAA NC_045512.2_19mer_win1_16836 16836 16854 506TGAAAAAGGTGACTATGGT 1709 ACCATAGTCACCTTTTTCANC_045512.2_19mer_win1_16837 16837 16855 507 GAAAAAGGTGACTATGGTG 1710CACCATAGTCACCTTTTTC NC_045512.2_19mer_win1_16838 16838 16856 508AAAAAGGTGACTATGGTGA 1711 TCACCATAGTCACCTTTTTNC_045512.2_19mer_win1_16839 16839 16857 509 AAAAGGTGACTATGGTGAT 1712ATCACCATAGTCACCTTTT NC_045512.2_19mer_win1_16840 16840 16858 510AAAGGTGACTATGGTGATG 1713 CATCACCATAGTCACCTTTNC_045512.2_19mer_win1_16841 16841 16859 511 AAGGTGACTATGGTGATGC 1714GCATCACCATAGTCACCTT NC_045512.2_19mer_win1_16842 16842 16860 512AGGTGACTATGGTGATGCT 1715 AGCATCACCATAGTCACCTNC_045512.2_19mer_win1_16843 16843 16861 513 GGTGACTATGGTGATGCTG 1716CAGCATCACCATAGTCACC NC_045512.2_19mer_win1_16844 16844 16862 514GTGACTATGGTGATGCTGT 1717 ACAGCATCACCATAGTCACNC_045512.2_19mer_win1_16845 16845 16863 515 TGACTATGGTGATGCTGTT 1718AACAGCATCACCATAGTCA NC_045512.2_19mer_win1_16846 16846 16864 516GACTATGGTGATGCTGTTG 1719 CAACAGCATCACCATAGTCNC_045512.2_19mer_win1_16847 16847 16865 517 ACTATGGTGATGCTGTTGT 1720ACAACAGCATCACCATAGT NC_045512.2_19mer_win1_16954 16954 16972 518CTAGTGCCACAAGAGCACT 1721 AGTGCTCTTGTGGCACTAGNC_045512.2_19mer_win1_16955 16955 16973 519 TAGTGCCACAAGAGCACTA 1722TAGTGCTCTTGTGGCACTA NC_045512.2_19mer_win1_16956 16956 16974 520AGTGCCACAAGAGCACTAT 1723 ATAGTGCTCTTGTGGCACTNC_045512.2_19mer_win1_16957 16957 16975 521 GTGCCACAAGAGCACTATG 1724CATAGTGCTCTTGTGGCAC NC_045512.2_19mer_win1_16958 16958 16976 522TGCCACAAGAGCACTATGT 1725 ACATAGTGCTCTTGTGGCANC_045512.2_19mer_win1_17008 17008 17026 523 ATCTCAGATGAGTTTTCTA 1726TAGAAAACTCATCTGAGAT NC_045512.2_19mer_win1_17009 17009 17027 524TCTCAGATGAGTTTTCTAG 1727 CTAGAAAACTCATCTGAGANC_045512.2_19mer_win1_17010 17010 17028 525 CTCAGATGAGTTTTCTAGC 1728GCTAGAAAACTCATCTGAG NC_045512.2_19mer_win1_17011 17011 17029 526TCAGATGAGTTTTCTAGCA 1729 TGCTAGAAAACTCATCTGANC_045512.2_19mer_win1_17012 17012 17030 527 CAGATGAGTTTTCTAGCAA 1730TTGCTAGAAAACTCATCTG NC_045512.2_19mer_win1_17013 17013 17031 528AGATGAGTTTTCTAGCAAT 1731 ATTGCTAGAAAACTCATCTNC_045512.2_19mer_win1_17014 17014 17032 529 GATGAGTTTTCTAGCAATG 1732CATTGCTAGAAAACTCATC NC_045512.2_19mer_win1_17015 17015 17033 530ATGAGTTTTCTAGCAATGT 1733 ACATTGCTAGAAAACTCATNC_045512.2_19mer_win1_17016 17016 17034 531 TGAGTTTTCTAGCAATGTT 1734AACATTGCTAGAAAACTCA NC_045512.2_19mer_win1_17017 17017 17035 532GAGTTTTCTAGCAATGTTG 1735 CAACATTGCTAGAAAACTCNC_045512.2_19mer_win1_17018 17018 17036 533 AGTTTTCTAGCAATGTTGC 1736GCAACATTGCTAGAAAACT NC_045512.2_19mer_win1_17019 17019 17037 534GTTTTCTAGCAATGTTGCA 1737 TGCAACATTGCTAGAAAACNC_045512.2_19mer_win1_17020 17020 17038 535 TTTTCTAGCAATGTTGCAA 1738TTGCAACATTGCTAGAAAA NC_045512.2_19mer_win1_17021 17021 17039 536TTTCTAGCAATGTTGCAAA 1739 TTTGCAACATTGCTAGAAANC_045512.2_19mer_win1_17022 17022 17040 537 TTCTAGCAATGTTGCAAAT 1740ATTTGCAACATTGCTAGAA NC_045512.2_19mer_win1_17023 17023 17041 538TCTAGCAATGTTGCAAATT 1741 AATTTGCAACATTGCTAGANC_045512.2_19mer_win1_17024 17024 17042 539 CTAGCAATGTTGCAAATTA 1742TAATTTGCAACATTGCTAG NC_045512.2_19mer_win1_17080 17080 17098 540GGACCACCTGGTACTGGTA 1743 TACCAGTACCAGGTGGTCCNC_045512.2_19mer_win1_17081 17081 17099 541 GACCACCTGGTACTGGTAA 1744TTACCAGTACCAGGTGGTC NC_045512.2_19mer_win1_17082 17082 17100 542ACCACCTGGTACTGGTAAG 1745 CTTACCAGTACCAGGTGGTNC_045512.2_19mer_win1_17083 17083 17101 543 CCACCTGGTACTGGTAAGA 1746TCTTACCAGTACCAGGTGG NC_045512.2_19mer_win1_17084 17084 17102 544CACCTGGTACTGGTAAGAG 1747 CTCTTACCAGTACCAGGTGNC_045512.2_19mer_win1_17085 17085 17103 545 ACCTGGTACTGGTAAGAGT 1748ACTCTTACCAGTACCAGGT NC_045512.2_19mer_win1_17086 17086 17104 546CCTGGTACTGGTAAGAGTC 1749 GACTCTTACCAGTACCAGGNC_045512.2_19mer_win1_17087 17087 17105 547 CTGGTACTGGTAAGAGTCA 1750TGACTCTTACCAGTACCAG NC_045512.2_19mer_win1_17088 17088 17106 548TGGTACTGGTAAGAGTCAT 1751 ATGACTCTTACCAGTACCANC_045512.2_19mer_win1_17089 17089 17107 549 GGTACTGGTAAGAGTCATT 1752AATGACTCTTACCAGTACC NC_045512.2_19mer_win1_17090 17090 17108 550GTACTGGTAAGAGTCATTT 1753 AAATGACTCTTACCAGTACNC_045512.2_19mer_win1_17091 17091 17109 551 TACTGGTAAGAGTCATTTT 1754AAAATGACTCTTACCAGTA NC_045512.2_19mer_win1_17092 17092 17110 552ACTGGTAAGAGTCATTTTG 1755 CAAAATGACTCTTACCAGTNC_045512.2_19mer_win1_17093 17093 17111 553 CTGGTAAGAGTCATTTTGC 1756GCAAAATGACTCTTACCAG NC_045512.2_19mer_win1_17137 17137 17155 554TCTGCTCGCATAGTGTATA 1757 TATACACTATGCGAGCAGANC_045512.2_19mer_win1_17138 17138 17156 555 CTGCTCGCATAGTGTATAC 1758GTATACACTATGCGAGCAG NC_045512.2_19mer_win1_17269 17269 17287 556AAATTCAAAGTGAATTCAA 1759 TTGAATTCACTTTGAATTTNC_045512.2_19mer_win1_17270 17270 17288 557 AATTCAAAGTGAATTCAAC 1760GTTGAATTCACTTTGAATT NC_045512.2_19mer_win1_17271 17271 17289 558ATTCAAAGTGAATTCAACA 1761 TGTTGAATTCACTTTGAATNC_045512.2_19mer_win1_17530 17530 17548 559 ATAGGTCCAGACATGTTCC 1762GGAACATGTCTGGACCTAT NC_045512.2_19mer_win1_17531 17531 17549 560TAGGTCCAGACATGTTCCT 1763 AGGAACATGTCTGGACCTANC_045512.2_19mer_win1_17563 17563 17581 561 CGTTGTCCTGCTGAAATTG 1764CAATTTCAGCAGGACAACG NC_045512.2_19mer_win1_17564 17564 17582 562GTTGTCCTGCTGAAATTGT 1765 ACAATTTCAGCAGGACAACNC_045512.2_19mer_win1_17680 17680 17698 563 CATGATGTTTCATCTGCAA 1766TTGCAGATGAAACATCATG NC_045512.2_19mer_win1_17681 17681 17699 564ATGATGTTTCATCTGCAAT 1767 ATTGCAGATGAAACATCATNC_045512.2_19mer_win1_17746 17746 17764 565 CCTGCTTGGAGAAAAGCTG 1768CAGCTTTTCTCCAAGCAGG NC_045512.2_19mer_win1_17747 17747 17765 566CTGCTTGGAGAAAAGCTGT 1769 ACAGCTTTTCTCCAAGCAGNC_045512.2_19mer_win1_17857 17857 17875 567 TATGACTATGTCATATTCA 1770TGAATATGACATAGTCATA NC_045512.2_19mer_win1_17858 17858 17876 568ATGACTATGTCATATTCAC 1771 GTGAATATGACATAGTCATNC_045512.2_19mer_win1_17956 17956 17974 569 TGCATAATGTCTGATAGAG 1772CTCTATCAGACATTATGCA NC_045512.2_19mer_win1_17957 17957 17975 570GCATAATGTCTGATAGAGA 1773 TCTCTATCAGACATTATGCNC_045512.2_19mer_win1_18100 18100 18118 571 ACACAGGCACCTACACACC 1774GGTGTGTAGGTGCCTGTGT NC_045512.2_19mer_win1_18101 18101 18119 572CACAGGCACCTACACACCT 1775 AGGTGTGTAGGTGCCTGTGNC_045512.2_19mer_win1_18102 18102 18120 573 ACAGGCACCTACACACCTC 1776GAGGTGTGTAGGTGCCTGT NC_045512.2_19mer_win1_18103 18103 18121 574CAGGCACCTACACACCTCA 1777 TGAGGTGTGTAGGTGCCTGNC_045512.2_19mer_win1_18104 18104 18122 575 AGGCACCTACACACCTCAG 1778CTGAGGTGTGTAGGTGCCT NC_045512.2_19mer_win1_18196 18196 18214 576AGACTCATCTCTATGATGG 1779 CCATCATAGAGATGAGTCTNC_045512.2_19mer_win1_18197 18197 18215 577 GACTCATCTCTATGATGGG 1780CCCATCATAGAGATGAGTC NC_045512.2_19mer_win1_18198 18198 18216 578ACTCATCTCTATGATGGGT 1781 ACCCATCATAGAGATGAGTNC_045512.2_19mer_win1_18199 18199 18217 579 CTCATCTCTATGATGGGTT 1782AACCCATCATAGAGATGAG NC_045512.2_19mer_win1_18200 18200 18218 580TCATCTCTATGATGGGTTT 1783 AAACCCATCATAGAGATGANC_045512.2_19mer_win1_19618 19618 19636 581 CAGAGTTTAGAAAATGTGG 1784CCACATTTTCTAAACTCTG NC_045512.2_19mer_win1_19619 19619 19637 582AGAGTTTAGAAAATGTGGC 1785 GCCACATTTTCTAAACTCTNC_045512.2_19mer_win1_19620 19620 19638 583 GAGTTTAGAAAATGTGGCT 1786AGCCACATTTTCTAAACTC NC_045512.2_19mer_win1_19621 19621 19639 584AGTTTAGAAAATGTGGCTT 1787 AAGCCACATTTTCTAAACTNC_045512.2_19mer_win1_19783 19783 19801 585 TTTGAGCTTTGGGCTAAGC 1788GCTTAGCCCAAAGCTCAAA NC_045512.2_19mer_win1_19784 19784 19802 586TTGAGCTTTGGGCTAAGCG 1789 CGCTTAGCCCAAAGCTCAANC_045512.2_19mer_win1_19831 19831 19849 587 ATACTCAATAATTTGGGTG 1790CACCCAAATTATTGAGTAT NC_045512.2_19mer_win1_19832 19832 19850 588TACTCAATAATTTGGGTGT 1791 ACACCCAAATTATTGAGTANC_045512.2_19mer_win1_20107 20107 20125 589 AATGGAGTCACATTAATTG 1792CAATTAATGTGACTCCATT NC_045512.2_19mer_win1_20108 20108 20126 590ATGGAGTCACATTAATTGG 1793 CCAATTAATGTGACTCCATNC_045512.2_19mer_win1_20109 20109 20127 591 TGGAGTCACATTAATTGGA 1794TCCAATTAATGTGACTCCA NC_045512.2_19mer_win1_20110 20110 20128 592GGAGTCACATTAATTGGAG 1795 CTCCAATTAATGTGACTCCNC_045512.2_19mer_win1_20111 20111 20129 593 GAGTCACATTAATTGGAGA 1796TCTCCAATTAATGTGACTC NC_045512.2_19mer_win1_20112 20112 20130 594AGTCACATTAATTGGAGAA 1797 TTCTCCAATTAATGTGACTNC_045512.2_19mer_win1_20776 20776 20794 595 ATAATGATGAATGTCGCAA 1798TTGCGACATTCATCATTAT NC_045512.2_19mer_win1_20777 20777 20795 596TAATGATGAATGTCGCAAA 1799 TTTGCGACATTCATCATTANC_045512.2_19mer_win1_21502 21502 21520 597 ATTAGAGAAAACAACAGAG 1800CTCTGTTGTTTTCTCTAAT NC_045512.2_19mer_win1_21503 21503 21521 598TTAGAGAAAACAACAGAGT 1801 ACTCTGTTGTTTTCTCTAANC_045512.2_19mer_win1_21504 21504 21522 599 TAGAGAAAACAACAGAGTT 1802AACTCTGTTGTTTTCTCTA NC_045512.2_19mer_win1_21505 21505 21523 600AGAGAAAACAACAGAGTTG 1803 CAACTCTGTTGTTTTCTCTNC_045512.2_19mer_win1_21506 21506 21524 601 GAGAAAACAACAGAGTTGT 1804ACAACTCTGTTGTTTTCTC NC_045512.2_19mer_win1_24302 24302 24320 602AATGTTCTCTATGAGAACC 1805 GGTTCTCATAGAGAACATTNC_045512.2_19mer_win1_24303 24303 24321 603 ATGTTCTCTATGAGAACCA 1806TGGTTCTCATAGAGAACAT NC_045512.2_19mer_win1_24304 24304 24322 604TGTTCTCTATGAGAACCAA 1807 TTGGTTCTCATAGAGAACANC_045512.2_19mer_win1_24305 24305 24323 605 GTTCTCTATGAGAACCAAA 1808TTTGGTTCTCATAGAGAAC NC_045512.2_19mer_win1_24306 24306 24324 606TTCTCTATGAGAACCAAAA 1809 TTTTGGTTCTCATAGAGAANC_045512.2_19mer_win1_24307 24307 24325 607 TCTCTATGAGAACCAAAAA 1810TTTTTGGTTCTCATAGAGA NC_045512.2_19mer_win1_24446 24446 24464 608CTTGTTAAACAACTTAGCT 1811 AGCTAAGTTGTTTAACAAGNC_045512.2_19mer_win1_24447 24447 24465 609 TTGTTAAACAACTTAGCTC 1812GAGCTAAGTTGTTTAACAA NC_045512.2_19mer_win1_24620 24620 24638 610GCTTCTGCTAATCTTGCTG 1813 CAGCAAGATTAGCAGAAGCNC_045512.2_19mer_win1_24621 24621 24639 611 CTTCTGCTAATCTTGCTGC 1814GCAGCAAGATTAGCAGAAG NC_045512.2_19mer_win1_24622 24622 24640 612TTCTGCTAATCTTGCTGCT 1815 AGCAGCAAGATTAGCAGAANC_045512.2_19mer_win1_24623 24623 24641 613 TCTGCTAATCTTGCTGCTA 1816TAGCAGCAAGATTAGCAGA NC_045512.2_19mer_win1_24624 24624 24642 614CTGCTAATCTTGCTGCTAC 1817 GTAGCAGCAAGATTAGCAGNC_045512.2_19mer_win1_24625 24625 24643 615 TGCTAATCTTGCTGCTACT 1818AGTAGCAGCAAGATTAGCA NC_045512.2_19mer_win1_24626 24626 24644 616GCTAATCTTGCTGCTACTA 1819 TAGTAGCAGCAAGATTAGCNC_045512.2_19mer_win1_24627 24627 24645 617 CTAATCTTGCTGCTACTAA 1820TTAGTAGCAGCAAGATTAG NC_045512.2_19mer_win1_24628 24628 24646 618TAATCTTGCTGCTACTAAA 1821 TTTAGTAGCAGCAAGATTANC_045512.2_19mer_win1_24629 24629 24647 619 AATCTTGCTGCTACTAAAA 1822TTTTAGTAGCAGCAAGATT NC_045512.2_19mer_win1_24630 24630 24648 620ATCTTGCTGCTACTAAAAT 1823 ATTTTAGTAGCAGCAAGATNC_045512.2_19mer_win1_24631 24631 24649 621 TCTTGCTGCTACTAAAATG 1824CATTTTAGTAGCAGCAAGA NC_045512.2_19mer_win1_24632 24632 24650 622CTTGCTGCTACTAAAATGT 1825 ACATTTTAGTAGCAGCAAGNC_045512.2_19mer_win1_24633 24633 24651 623 TTGCTGCTACTAAAATGTC 1826GACATTTTAGTAGCAGCAA NC_045512.2_19mer_win1_24662 24662 24680 624CTTGGACAATCAAAAAGAG 1827 CTCTTTTTGATTGTCCAAGNC_045512.2_19mer_win1_24663 24663 24681 625 TTGGACAATCAAAAAGAGT 1828ACTCTTTTTGATTGTCCAA NC_045512.2_19mer_win1_24664 24664 24682 626TGGACAATCAAAAAGAGTT 1829 AACTCTTTTTGATTGTCCANC_045512.2_19mer_win1_24665 24665 24683 627 GGACAATCAAAAAGAGTTG 1830CAACTCTTTTTGATTGTCC NC_045512.2_19mer_win1_24666 24666 24684 628GACAATCAAAAAGAGTTGA 1831 TCAACTCTTTTTGATTGTCNC_045512.2_19mer_win1_25034 25034 25052 629 AATCATACATCACCAGATG 1832CATCTGGTGATGTATGATT NC_045512.2_19mer_win1_25035 25035 25053 630ATCATACATCACCAGATGT 1833 ACATCTGGTGATGTATGATNC_045512.2_19mer_win1_25038 25038 25056 633 ATACATCACCAGATGTTGA 1836TCAACATCTGGTGATGTAT NC_045512.2_19mer_win1_25039 25039 25057 634TACATCACCAGATGTTGAT 1837 ATCAACATCTGGTGATGTANC_045512.2_19mer_win1_25104 25104 25122 635 AAGAAATTGACCGCCTCAA 1838TTGAGGCGGTCAATTTCTT NC_045512.2_19mer_win1_25105 25105 25123 636AGAAATTGACCGCCTCAAT 1839 ATTGAGGCGGTCAATTTCTNC_045512.2_19mer_win1_25106 25106 25124 637 GAAATTGACCGCCTCAATG 1840CATTGAGGCGGTCAATTTC NC_045512.2_19mer_win1_25107 25107 25125 638AAATTGACCGCCTCAATGA 1841 TCATTGAGGCGGTCAATTTNC_045512.2_19mer_win1_25108 25108 25126 639 AATTGACCGCCTCAATGAG 1842CTCATTGAGGCGGTCAATT NC_045512.2_19mer_win1_25109 25109 25127 640ATTGACCGCCTCAATGAGG 1843 CCTCATTGAGGCGGTCAATNC_045512.2_19mer_win1_25110 25110 25128 641 TTGACCGCCTCAATGAGGT 1844ACCTCATTGAGGCGGTCAA NC_045512.2_19mer_win1_25364 25364 25382 642GTCAAATTACATTACACAT 1845 ATGTGTAATGTAATTTGACNC_045512.2_19mer_win1_25365 25365 25383 643 TCAAATTACATTACACATA 1846TATGTGTAATGTAATTTGA NC_045512.2_19mer_win1_25366 25366 25384 644CAAATTACATTACACATAA 1847 TTATGTGTAATGTAATTTGNC_045512.2_19mer_win1_25367 25367 25385 645 AAATTACATTACACATAAA 1848TTTATGTGTAATGTAATTT NC_045512.2_19mer_win1_25368 25368 25386 646AATTACATTACACATAAAC 1849 GTTTATGTGTAATGTAATTNC_045512.2_19mer_win1_25369 25369 25387 647 ATTACATTACACATAAACG 1850CGTTTATGTGTAATGTAAT NC_045512.2_19mer_win1_25502 25502 25520 648TACAAGCCTCACTCCCTTT 1851 AAAGGGAGTGAGGCTTGTANC_045512.2_19mer_win1_25503 25503 25521 649 ACAAGCCTCACTCCCTTTC 1852GAAAGGGAGTGAGGCTTGT NC_045512.2_19mer_win1_25504 25504 25522 650CAAGCCTCACTCCCTTTCG 1853 CGAAAGGGAGTGAGGCTTGNC_045512.2_19mer_win1_25505 25505 25523 651 AAGCCTCACTCCCTTTCGG 1854CCGAAAGGGAGTGAGGCTT NC_045512.2_19mer_win1_25506 25506 25524 652AGCCTCACTCCCTTTCGGA 1855 TCCGAAAGGGAGTGAGGCTNC_045512.2_19mer_win1_25507 25507 25525 653 GCCTCACTCCCTTTCGGAT 1856ATCCGAAAGGGAGTGAGGC NC_045512.2_19mer_win1_25508 25508 25526 654CCTCACTCCCTTTCGGATG 1857 CATCCGAAAGGGAGTGAGGNC_045512.2_19mer_win1_25509 25509 25527 655 CTCACTCCCTTTCGGATGG 1858CCATCCGAAAGGGAGTGAG NC_045512.2_19mer_win1_25510 25510 25528 656TCACTCCCTTTCGGATGGC 1859 GCCATCCGAAAGGGAGTGANC_045512.2_19mer_win1_25511 25511 25529 657 CACTCCCTTTCGGATGGCT 1860AGCCATCCGAAAGGGAGTG NC_045512.2_19mer_win1_25512 25512 25530 658ACTCCCTTTCGGATGGCTT 1861 AAGCCATCCGAAAGGGAGTNC_045512.2_19mer_win1_26191 26191 26209 659 CCGACGACGACTACTAGCG 1862CGCTAGTAGTCGTCGTCGG NC_045512.2_19mer_win1_26192 26192 26210 660CGACGACGACTACTAGCGT 1863 ACGCTAGTAGTCGTCGTCGNC_045512.2_19mer_win1_26193 26193 26211 661 GACGACGACTACTAGCGTG 1864CACGCTAGTAGTCGTCGTC NC_045512.2_19mer_win1_26194 26194 26212 662ACGACGACTACTAGCGTGC 1865 GCACGCTAGTAGTCGTCGTNC_045512.2_19mer_win1_26195 26195 26213 663 CGACGACTACTAGCGTGCC 1866GGCACGCTAGTAGTCGTCG NC_045512.2_19mer_win1_26196 26196 26214 664GACGACTACTAGCGTGCCT 1867 AGGCACGCTAGTAGTCGTCNC_045512.2_19mer_win1_26197 26197 26215 665 ACGACTACTAGCGTGCCTT 1868AAGGCACGCTAGTAGTCGT NC_045512.2_19mer_win1_26198 26198 26216 666CGACTACTAGCGTGCCTTT 1869 AAAGGCACGCTAGTAGTCGNC_045512.2_19mer_win1_26199 26199 26217 667 GACTACTAGCGTGCCTTTG 1870CAAAGGCACGCTAGTAGTC NC_045512.2_19mer_win1_26200 26200 26218 668ACTACTAGCGTGCCTTTGT 1871 ACAAAGGCACGCTAGTAGTNC_045512.2_19mer_win1_26201 26201 26219 669 CTACTAGCGTGCCTTTGTA 1872TACAAAGGCACGCTAGTAG NC_045512.2_19mer_win1_26202 26202 26220 670TACTAGCGTGCCTTTGTAA 1873 TTACAAAGGCACGCTAGTANC_045512.2_19mer_win1_26203 26203 26221 671 ACTAGCGTGCCTTTGTAAG 1874CTTACAAAGGCACGCTAGT NC_045512.2_19mer_win1_26204 26204 26222 672CTAGCGTGCCTTTGTAAGC 1875 GCTTACAAAGGCACGCTAGNC_045512.2_19mer_win1_26205 26205 26223 673 TAGCGTGCCTTTGTAAGCA 1876TGCTTACAAAGGCACGCTA NC_045512.2_19mer_win1_26206 26206 26224 674AGCGTGCCTTTGTAAGCAC 1877 GTGCTTACAAAGGCACGCTNC_045512.2_19mer_win1_26207 26207 26225 675 GCGTGCCTTTGTAAGCACA 1878TGTGCTTACAAAGGCACGC NC_045512.2_19mer_win1_26208 26208 26226 676CGTGCCTTTGTAAGCACAA 1879 TTGTGCTTACAAAGGCACGNC_045512.2_19mer_win1_26209 26209 26227 677 GTGCCTTTGTAAGCACAAG 1880CTTGTGCTTACAAAGGCAC NC_045512.2_19mer_win1_26232 26232 26250 678TGAGTACGAACTTATGTAC 1881 GTACATAAGTTCGTACTCANC_045512.2_19mer_win1_26233 26233 26251 679 GAGTACGAACTTATGTACT 1882AGTACATAAGTTCGTACTC NC_045512.2_19mer_win1_26234 26234 26252 680AGTACGAACTTATGTACTC 1883 GAGTACATAAGTTCGTACTNC_045512.2_19mer_win1_26235 26235 26253 681 GTACGAACTTATGTACTCA 1884TGAGTACATAAGTTCGTAC NC_045512.2_19mer_win1_26236 26236 26254 682TACGAACTTATGTACTCAT 1885 ATGAGTACATAAGTTCGTANC_045512.2_19mer_win1_26237 26237 26255 683 ACGAACTTATGTACTCATT 1886AATGAGTACATAAGTTCGT NC_045512.2_19mer_win1_26238 26238 26256 684CGAACTTATGTACTCATTC 1887 GAATGAGTACATAAGTTCGNC_045512.2_19mer_win1_26239 26239 26257 685 GAACTTATGTACTCATTCG 1888CGAATGAGTACATAAGTTC NC_045512.2_19mer_win1_26240 26240 26258 686AACTTATGTACTCATTCGT 1889 ACGAATGAGTACATAAGTTNC_045512.2_19mer_win1_26241 26241 26259 687 ACTTATGTACTCATTCGTT 1890AACGAATGAGTACATAAGT NC_045512.2_19mer_win1_26242 26242 26260 688CTTATGTACTCATTCGTTT 1891 AAACGAATGAGTACATAAGNC_045512.2_19mer_win1_26243 26243 26261 689 TTATGTACTCATTCGTTTC 1892GAAACGAATGAGTACATAA NC_045512.2_19mer_win1_26244 26244 26262 690TATGTACTCATTCGTTTCG 1893 CGAAACGAATGAGTACATANC_045512.2_19mer_win1_26245 26245 26263 691 ATGTACTCATTCGTTTCGG 1894CCGAAACGAATGAGTACAT NC_045512.2_19mer_win1_26246 26246 26264 692TGTACTCATTCGTTTCGGA 1895 TCCGAAACGAATGAGTACANC_045512.2_19mer_win1_26247 26247 26265 693 GTACTCATTCGTTTCGGAA 1896TTCCGAAACGAATGAGTAC NC_045512.2_19mer_win1_26248 26248 26266 694TACTCATTCGTTTCGGAAG 1897 CTTCCGAAACGAATGAGTANC_045512.2_19mer_win1_26249 26249 26267 695 ACTCATTCGTTTCGGAAGA 1898TCTTCCGAAACGAATGAGT NC_045512.2_19mer_win1_26269 26269 26287 696ACAGGTACGTTAATAGTTA 1899 TAACTATTAACGTACCTGTNC_045512.2_19mer_win1_26270 26270 26288 697 CAGGTACGTTAATAGTTAA 1900TTAACTATTAACGTACCTG NC_045512.2_19mer_win1_26271 26271 26289 698AGGTACGTTAATAGTTAAT 1901 ATTAACTATTAACGTACCTNC_045512.2_19mer_win1_26272 26272 26290 699 GGTACGTTAATAGTTAATA 1902TATTAACTATTAACGTACC NC_045512.2_19mer_win1_26273 26273 26291 700GTACGTTAATAGTTAATAG 1903 CTATTAACTATTAACGTACNC_045512.2_19mer_win1_26274 26274 26292 701 TACGTTAATAGTTAATAGC 1904GCTATTAACTATTAACGTA NC_045512.2_19mer_win1_26275 26275 26293 702ACGTTAATAGTTAATAGCG 1905 CGCTATTAACTATTAACGTNC_045512.2_19mer_win1_26276 26276 26294 703 CGTTAATAGTTAATAGCGT 1906ACGCTATTAACTATTAACG NC_045512.2_19mer_win1_26277 26277 26295 704GTTAATAGTTAATAGCGTA 1907 TACGCTATTAACTATTAACNC_045512.2_19mer_win1_26278 26278 26296 705 TTAATAGTTAATAGCGTAC 1908GTACGCTATTAACTATTAA NC_045512.2_19mer_win1_26279 26279 26297 706TAATAGTTAATAGCGTACT 1909 AGTACGCTATTAACTATTANC_045512.2_19mer_win1_26280 26280 26298 707 AATAGTTAATAGCGTACTT 1910AAGTACGCTATTAACTATT NC_045512.2_19mer_win1_26281 26281 26299 708ATAGTTAATAGCGTACTTC 1911 GAAGTACGCTATTAACTATNC_045512.2_19mer_win1_26282 26282 26300 709 TAGTTAATAGCGTACTTCT 1912AGAAGTACGCTATTAACTA NC_045512.2_19mer_win1_26283 26283 26301 710AGTTAATAGCGTACTTCTT 1913 AAGAAGTACGCTATTAACTNC_045512.2_19mer_win1_26284 26284 26302 711 GTTAATAGCGTACTTCTTT 1914AAAGAAGTACGCTATTAAC NC_045512.2_19mer_win1_26285 26285 26303 712TTAATAGCGTACTTCTTTT 1915 AAAAGAAGTACGCTATTAANC_045512.2_19mer_win1_26286 26286 26304 713 TAATAGCGTACTTCTTTTT 1916AAAAAGAAGTACGCTATTA NC_045512.2_19mer_win1_26287 26287 26305 714AATAGCGTACTTCTTTTTC 1917 GAAAAAGAAGTACGCTATTNC_045512.2_19mer_win1_26288 26288 26306 715 ATAGCGTACTTCTTTTTCT 1918AGAAAAAGAAGTACGCTAT NC_045512.2_19mer_win1_26289 26289 26307 716TAGCGTACTTCTTTTTCTT 1919 AAGAAAAAGAAGTACGCTANC_045512.2_19mer_win1_26290 26290 26308 717 AGCGTACTTCTTTTTCTTG 1920CAAGAAAAAGAAGTACGCT NC_045512.2_19mer_win1_26291 26291 26309 718GCGTACTTCTTTTTCTTGC 1921 GCAAGAAAAAGAAGTACGCNC_045512.2_19mer_winl_26292 26292 26310 719 CGTACTTCTTTTTCTTGCT 1922AGCAAGAAAAAGAAGTACG NC_045512.2_19mer_winl_26293 26293 26311 720GTACTTCTTTTTCTTGCTT 1923 AAGCAAGAAAAAGAAGTACNC_045512.2_19mer_winl_26294 26294 26312 721 TACTTCTTTTTCTTGCTTT 1924AAAGCAAGAAAAAGAAGTA NC_045512.2_19mer_winl_26295 26295 26313 722ACTTCTTTTTCTTGCTTTC 1925 GAAAGCAAGAAAAAGAAGTNC_045512.2_19mer_winl_26296 26296 26314 723 CTTCTTTTTCTTGCTTTCG 1926CGAAAGCAAGAAAAAGAAG NC_045512.2_19mer_winl_26297 26297 26315 724TTCTTTTTCTTGCTTTCGT 1927 ACGAAAGCAAGAAAAAGAANC_045512.2_19mer_winl_26298 26298 26316 725 TCTTTTTCTTGCTTTCGTG 1928CACGAAAGCAAGAAAAAGA NC_045512.2_19mer_winl_26299 26299 26317 726CTTTTTCTTGCTTTCGTGG 1929 CCACGAAAGCAAGAAAAAGNC_045512.2_19mer_winl_26300 26300 26318 727 TTTTTCTTGCTTTCGTGGT 1930ACCACGAAAGCAAGAAAAA NC_045512.2_19mer_winl_26301 26301 26319 728TTTTCTTGCTTTCGTGGTA 1931 TACCACGAAAGCAAGAAAANC_045512.2_19mer_winl_26302 26302 26320 729 TTTCTTGCTTTCGTGGTAT 1932ATACCACGAAAGCAAGAAA NC_045512.2_19mer_winl_26303 26303 26321 730TTCTTGCTTTCGTGGTATT 1933 AATACCACGAAAGCAAGAANC_045512.2_19mer_winl_26304 26304 26322 731 TCTTGCTTTCGTGGTATTC 1934GAATACCACGAAAGCAAGA NC_045512.2_19mer_winl_26305 26305 26323 732CTTGCTTTCGTGGTATTCT 1935 AGAATACCACGAAAGCAAGNC_045512.2_19mer_winl_26306 26306 26324 733 TTGCTTTCGTGGTATTCTT 1936AAGAATACCACGAAAGCAA NC_045512.2_19mer_winl_26307 26307 26325 734TGCTTTCGTGGTATTCTTG 1937 CAAGAATACCACGAAAGCANC_045512.2_19mer_winl_26308 26308 26326 735 GCTTTCGTGGTATTCTTGC 1938GCAAGAATACCACGAAAGC NC_045512.2_19mer_winl_26309 26309 26327 736CTTTCGTGGTATTCTTGCT 1939 AGCAAGAATACCACGAAAGNC_045512.2_19mer_winl_26310 26310 26328 737 TTTCGTGGTATTCTTGCTA 1940TAGCAAGAATACCACGAAA NC_045512.2_19mer_winl_26311 26311 26329 738TTCGTGGTATTCTTGCTAG 1941 CTAGCAAGAATACCACGAANC_045512.2_19mer_win1_26312 26312 26330 739 TCGTGGTATTCTTGCTAGT 1942ACTAGCAAGAATACCACGA NC_045512.2_19mer_win1_26332 26332 26350 740ACACTAGCCATCCTTACTG 1943 CAGTAAGGATGGCTAGTGTNC_045512.2_19mer_win1_26333 26333 26351 741 CACTAGCCATCCTTACTGC 1944GCAGTAAGGATGGCTAGTG NC_045512.2_19mer_win1_26334 26334 26352 742ACTAGCCATCCTTACTGCG 1945 CGCAGTAAGGATGGCTAGTNC_045512.2_19mer_win1_26335 26335 26353 743 CTAGCCATCCTTACTGCGC 1946GCGCAGTAAGGATGGCTAG NC_045512.2_19mer_win1_26336 26336 26354 744TAGCCATCCTTACTGCGCT 1947 AGCGCAGTAAGGATGGCTANC_045512.2_19mer_win1_26337 26337 26355 745 AGCCATCCTTACTGCGCTT 1948AAGCGCAGTAAGGATGGCT NC_045512.2_19mer_win1_26338 26338 26356 746GCCATCCTTACTGCGCTTC 1949 GAAGCGCAGTAAGGATGGCNC_045512.2_19mer_win1_26339 26339 26357 747 CCATCCTTACTGCGCTTCG 1950CGAAGCGCAGTAAGGATGG NC_045512.2_19mer_win1_26340 26340 26358 748CATCCTTACTGCGCTTCGA 1951 TCGAAGCGCAGTAAGGATGNC_045512.2_19mer_win1_26341 26341 26359 749 ATCCTTACTGCGCTTCGAT 1952ATCGAAGCGCAGTAAGGAT NC_045512.2_19mer_win1_26342 26342 26360 750TCCTTACTGCGCTTCGATT 1953 AATCGAAGCGCAGTAAGGANC_045512.2_19mer_win1_26343 26343 26361 751 CCTTACTGCGCTTCGATTG 1954CAATCGAAGCGCAGTAAGG NC_045512.2_19mer_win1_26344 26344 26362 752CTTACTGCGCTTCGATTGT 1955 ACAATCGAAGCGCAGTAAGNC_045512.2_19mer_win1_26345 26345 26363 753 TTACTGCGCTTCGATTGTG 1956CACAATCGAAGCGCAGTAA NC_045512.2_19mer_win1_26346 26346 26364 754TACTGCGCTTCGATTGTGT 1957 ACACAATCGAAGCGCAGTANC_045512.2_19mer_win1_26347 26347 26365 755 ACTGCGCTTCGATTGTGTG 1958CACACAATCGAAGCGCAGT NC_045512.2_19mer_win1_26348 26348 26366 756CTGCGCTTCGATTGTGTGC 1959 GCACACAATCGAAGCGCAGNC_045512.2_19mer_win1_26349 26349 26367 757 TGCGCTTCGATTGTGTGCG 1960CGCACACAATCGAAGCGCA NC_045512.2_19mer_win1_26350 26350 26368 758GCGCTTCGATTGTGTGCGT 1961 ACGCACACAATCGAAGCGCNC_045512.2_19mer_win1_26351 26351 26369 759 CGCTTCGATTGTGTGCGTA 1962TACGCACACAATCGAAGCG NC_045512.2_19mer_win1_26352 26352 26370 760GCTTCGATTGTGTGCGTAC 1963 GTACGCACACAATCGAAGCNC_045512.2_19mer_win1_26353 26353 26371 761 CTTCGATTGTGTGCGTACT 1964AGTACGCACACAATCGAAG NC_045512.2_19mer_win1_26354 26354 26372 762TTCGATTGTGTGCGTACTG 1965 CAGTACGCACACAATCGAANC_045512.2_19mer_win1_26355 26355 26373 763 TCGATTGTGTGCGTACTGC 1966GCAGTACGCACACAATCGA NC_045512.2_19mer_win1_26356 26356 26374 764CGATTGTGTGCGTACTGCT 1967 AGCAGTACGCACACAATCGNC_045512.2_19mer_win1_26357 26357 26375 765 GATTGTGTGCGTACTGCTG 1968CAGCAGTACGCACACAATC NC_045512.2_19mer_win1_26358 26358 26376 766ATTGTGTGCGTACTGCTGC 1969 GCAGCAGTACGCACACAATNC_045512.2_19mer_win1_26359 26359 26377 767 TTGTGTGCGTACTGCTGCA 1970TGCAGCAGTACGCACACAA NC_045512.2_19mer_win1_26360 26360 26378 768TGTGTGCGTACTGCTGCAA 1971 TTGCAGCAGTACGCACACANC_045512.2_19mer_win1_26361 26361 26379 769 GTGTGCGTACTGCTGCAAT 1972ATTGCAGCAGTACGCACAC NC_045512.2_19mer_win1_26362 26362 26380 770TGTGCGTACTGCTGCAATA 1973 TATTGCAGCAGTACGCACANC_045512.2_19mer_win1_26363 26363 26381 771 GTGCGTACTGCTGCAATAT 1974ATATTGCAGCAGTACGCAC NC_045512.2_19mer_win1_26364 26364 26382 772TGCGTACTGCTGCAATATT 1975 AATATTGCAGCAGTACGCANC_045512.2_19mer_win1_26365 26365 26383 773 GCGTACTGCTGCAATATTG 1976CAATATTGCAGCAGTACGC NC_045512.2_19mer_win1_26366 26366 26384 774CGTACTGCTGCAATATTGT 1977 ACAATATTGCAGCAGTACGNC_045512.2_19mer_win1_26367 26367 26385 775 GTACTGCTGCAATATTGTT 1978AACAATATTGCAGCAGTAC NC_045512.2_19mer_win1_26368 26368 26386 776TACTGCTGCAATATTGTTA 1979 TAACAATATTGCAGCAGTANC_045512.2_19mer_win1_26369 26369 26387 777 ACTGCTGCAATATTGTTAA 1980TTAACAATATTGCAGCAGT NC_045512.2_19mer_win1_26370 26370 26388 778CTGCTGCAATATTGTTAAC 1981 GTTAACAATATTGCAGCAGNC_045512.2_19mer_win1_26371 26371 26389 779 TGCTGCAATATTGTTAACG 1982CGTTAACAATATTGCAGCA NC_045512.2_19mer_win1_26372 26372 26390 780GCTGCAATATTGTTAACGT 1983 ACGTTAACAATATTGCAGCNC_045512.2_19mer_win1_26373 26373 26391 781 CTGCAATATTGTTAACGTG 1984CACGTTAACAATATTGCAG NC_045512.2_19mer_win1_26374 26374 26392 782TGCAATATTGTTAACGTGA 1985 TCACGTTAACAATATTGCANC_045512.2_19mer_win1_26375 26375 26393 783 GCAATATTGTTAACGTGAG 1986CTCACGTTAACAATATTGC NC_045512.2_19mer_win1_26376 26376 26394 784CAATATTGTTAACGTGAGT 1987 ACTCACGTTAACAATATTGNC_045512.2_19mer_win1_26450 26450 26468 785 GAGTTCCTGATCTTCTGGT 1988ACCAGAAGATCAGGAACTC NC_045512.2_19mer_win1_26451 26451 26469 786AGTTCCTGATCTTCTGGTC 1989 GACCAGAAGATCAGGAACTNC_045512.2_19mer_win1_26452 26452 26470 787 GTTCCTGATCTTCTGGTCT 1990AGACCAGAAGATCAGGAAC NC_045512.2_19mer_win1_26453 26453 26471 788TTCCTGATCTTCTGGTCTA 1991 TAGACCAGAAGATCAGGAANC_045512.2_19mer_win1_26454 26454 26472 789 TCCTGATCTTCTGGTCTAA 1992TTAGACCAGAAGATCAGGA NC_045512.2_19mer_win1_26455 26455 26473 790CCTGATCTTCTGGTCTAAA 1993 TTTAGACCAGAAGATCAGGNC_045512.2_19mer_win1_26456 26456 26474 791 CTGATCTTCTGGTCTAAAC 1994GTTTAGACCAGAAGATCAG NC_045512.2_19mer_win1_26457 26457 26475 792TGATCTTCTGGTCTAAACG 1995 CGTTTAGACCAGAAGATCANC_045512.2_19mer_win1_26458 26458 26476 793 GATCTTCTGGTCTAAACGA 1996TCGTTTAGACCAGAAGATC NC_045512.2_19mer_win1_26459 26459 26477 794ATCTTCTGGTCTAAACGAA 1997 TTCGTTTAGACCAGAAGATNC_045512.2_19mer_win1_26460 26460 26478 795 TCTTCTGGTCTAAACGAAC 1998GTTCGTTTAGACCAGAAGA NC_045512.2_19mer_win1_26461 26461 26479 796CTTCTGGTCTAAACGAACT 1999 AGTTCGTTTAGACCAGAAGNC_045512.2_19mer_win1_26462 26462 26480 797 TTCTGGTCTAAACGAACTA 2000TAGTTCGTTTAGACCAGAA NC_045512.2_19mer_win1_26463 26463 26481 798TCTGGTCTAAACGAACTAA 2001 TTAGTTCGTTTAGACCAGANC_045512.2_19mer_win1_26574 26574 26592 799 GAACAATGGAACCTAGTAA 2002TTACTAGGTTCCATTGTTC NC_045512.2_19mer_win1_26575 26575 26593 800AACAATGGAACCTAGTAAT 2003 ATTACTAGGTTCCATTGTTNC_045512.2_19mer_win1_26576 26576 26594 801 ACAATGGAACCTAGTAATA 2004TATTACTAGGTTCCATTGT NC_045512.2_19mer_win1_26577 26577 26595 802CAATGGAACCTAGTAATAG 2005 CTATTACTAGGTTCCATTGNC_045512.2_19mer_win1_26578 26578 26596 803 AATGGAACCTAGTAATAGG 2006CCTATTACTAGGTTCCATT NC_045512.2_19mer_win1_26579 26579 26597 804ATGGAACCTAGTAATAGGT 2007 ACCTATTACTAGGTTCCATNC_045512.2_19mer_win1_26580 26580 26598 805 TGGAACCTAGTAATAGGTT 2008AACCTATTACTAGGTTCCA NC_045512.2_19mer_win1_26581 26581 26599 806GGAACCTAGTAATAGGTTT 2009 AAACCTATTACTAGGTTCCNC_045512.2_19mer_win1_26582 26582 26600 807 GAACCTAGTAATAGGTTTC 2010GAAACCTATTACTAGGTTC NC_045512.2_19mer_win1_27033 27033 27051 808GCTACATCACGAACGCTTT 2011 AAAGCGTTCGTGATGTAGCNC_045512.2_19mer_win1_27034 27034 27052 809 CTACATCACGAACGCTTTC 2012GAAAGCGTTCGTGATGTAG NC_045512.2_19mer_win1_27035 27035 27053 810TACATCACGAACGCTTTCT 2013 AGAAAGCGTTCGTGATGTANC_045512.2_19mer_win1_27036 27036 27054 811 ACATCACGAACGCTTTCTT 2014AAGAAAGCGTTCGTGATGT NC_045512.2_19mer_win1_27037 27037 27055 812CATCACGAACGCTTTCTTA 2015 TAAGAAAGCGTTCGTGATGNC_045512.2_19mer_win1_27038 27038 27056 813 ATCACGAACGCTTTCTTAT 2016ATAAGAAAGCGTTCGTGAT NC_045512.2_19mer_win1_27039 27039 27057 814TCACGAACGCTTTCTTATT 2017 AATAAGAAAGCGTTCGTGANC_045512.2_19mer_win1_27040 27040 27058 815 CACGAACGCTTTCTTATTA 2018TAATAAGAAAGCGTTCGTG NC_045512.2_19mer_win1_27041 27041 27059 816ACGAACGCTTTCTTATTAC 2019 GTAATAAGAAAGCGTTCGTNC_045512.2_19mer_win1_27042 27042 27060 817 CGAACGCTTTCTTATTACA 2020TGTAATAAGAAAGCGTTCG NC_045512.2_19mer_win1_27043 27043 27061 818GAACGCTTTCTTATTACAA 2021 TTGTAATAAGAAAGCGTTCNC_045512.2_19mer_win1_27044 27044 27062 819 AACGCTTTCTTATTACAAA 2022TTTGTAATAAGAAAGCGTT NC_045512.2_19mer_win1_27045 27045 27063 820ACGCTTTCTTATTACAAAT 2023 ATTTGTAATAAGAAAGCGTNC_045512.2_19mer_win1_27046 27046 27064 821 CGCTTTCTTATTACAAATT 2024AATTTGTAATAAGAAAGCG NC_045512.2_19mer_win1_27093 27093 27111 822TCAGGTTTTGCTGCATACA 2025 TGTATGCAGCAAAACCTGANC_045512.2_19mer_win1_27183 27183 27201 823 GTACAGTAAGTGACAACAG 2026CTGTTGTCACTTACTGTAC NC_045512.2_19mer_win1_27184 27184 27202 824TACAGTAAGTGACAACAGA 2027 TCTGTTGTCACTTACTGTANC_045512.2_19mer_win1_27185 27185 27203 825 ACAGTAAGTGACAACAGAT 2028ATCTGTTGTCACTTACTGT NC_045512.2_19mer_win1_27186 27186 27204 826CAGTAAGTGACAACAGATG 2029 CATCTGTTGTCACTTACTGNC_045512.2_19mer_win1_27187 27187 27205 827 AGTAAGTGACAACAGATGT 2030ACATCTGTTGTCACTTACT NC_045512.2_19mer_win1_27188 27188 27206 828GTAAGTGACAACAGATGTT 2031 AACATCTGTTGTCACTTACNC_045512.2_19mer_win1_27189 27189 27207 829 TAAGTGACAACAGATGTTT 2032AAACATCTGTTGTCACTTA NC_045512.2_19mer_win1_27190 27190 27208 830AAGTGACAACAGATGTTTC 2033 GAAACATCTGTTGTCACTTNC_045512.2_19mer_win1_27191 27191 27209 831 AGTGACAACAGATGTTTCA 2034TGAAACATCTGTTGTCACT NC_045512.2_19mer_win1_27192 27192 27210 832GTGACAACAGATGTTTCAT 2035 ATGAAACATCTGTTGTCACNC_045512.2_19mer_win1_27193 27193 27211 833 TGACAACAGATGTTTCATC 2036GATGAAACATCTGTTGTCA NC_045512.2_19mer_win1_27194 27194 27212 834GACAACAGATGTTTCATCT 2037 AGATGAAACATCTGTTGTCNC_045512.2_19mer_win1_27382 27382 27400 835 GATTAAACGAACATGAAAA 2038TTTTCATGTTCGTTTAATC NC_045512.2_19mer_win1_27383 27383 27401 836ATTAAACGAACATGAAAAT 2039 ATTTTCATGTTCGTTTAATNC_045512.2_19mer_win1_27384 27384 27402 837 TTAAACGAACATGAAAATT 2040AATTTTCATGTTCGTTTAA NC_045512.2_19mer_win1_27385 27385 27403 838TAAACGAACATGAAAATTA 2041 TAATTTTCATGTTCGTTTANC_045512.2_19mer_win1_27386 27386 27404 839 AAACGAACATGAAAATTAT 2042ATAATTTTCATGTTCGTTT NC_045512.2_19mer_win1_27387 27387 27405 840AACGAACATGAAAATTATT 2043 AATAATTTTCATGTTCGTTNC_045512.2_19mer_win1_27388 27388 27406 841 ACGAACATGAAAATTATTC 2044GAATAATTTTCATGTTCGT NC_045512.2_19mer_win1_27389 27389 27407 842CGAACATGAAAATTATTCT 2045 AGAATAATTTTCATGTTCGNC_045512.2_19mer_win1_27511 27511 27529 843 TACGAGGGCAATTCACCAT 2046ATGGTGAATTGCCCTCGTA NC_045512.2_19mer_win1_27512 27512 27530 844ACGAGGGCAATTCACCATT 2047 AATGGTGAATTGCCCTCGTNC_045512.2_19mer_win1_27513 27513 27531 845 CGAGGGCAATTCACCATTT 2048AAATGGTGAATTGCCCTCG NC_045512.2_19mer_win1_27514 27514 27532 846GAGGGCAATTCACCATTTC 2049 GAAATGGTGAATTGCCCTCNC_045512.2_19mer_win1_27515 27515 27533 847 AGGGCAATTCACCATTTCA 2050TGAAATGGTGAATTGCCCT NC_045512.2_19mer_win1_27771 27771 27789 848TTAATTGACTTCTATTTGT 2051 ACAAATAGAAGTCAATTAANC_045512.2_19mer_win1_27772 27772 27790 849 TAATTGACTTCTATTTGTG 2052CACAAATAGAAGTCAATTA NC_045512.2_19mer_win1_27773 27773 27791 850AATTGACTTCTATTTGTGC 2053 GCACAAATAGAAGTCAATTNC_045512.2_19mer_win1_27774 27774 27792 851 ATTGACTTCTATTTGTGCT 2054AGCACAAATAGAAGTCAAT NC_045512.2_19mer_win1_27775 27775 27793 852TTGACTTCTATTTGTGCTT 2055 AAGCACAAATAGAAGTCAANC_045512.2_19mer_win1_27776 27776 27794 853 TGACTTCTATTTGTGCTTT 2056AAAGCACAAATAGAAGTCA NC_045512.2_19mer_win1_27777 27777 27795 854GACTTCTATTTGTGCTTTT 2057 AAAAGCACAAATAGAAGTCNC_045512.2_19mer_win1_27778 27778 27796 855 ACTTCTATTTGTGCTTTTT 2058AAAAAGCACAAATAGAAGT NC_045512.2_19mer_win1_27779 27779 27797 856CTTCTATTTGTGCTTTTTA 2059 TAAAAAGCACAAATAGAAGNC_045512.2_19mer_win1_27780 27780 27798 857 TTCTATTTGTGCTTTTTAG 2060CTAAAAAGCACAAATAGAA NC_045512.2_19mer_win1_27781 27781 27799 858TCTATTTGTGCTTTTTAGC 2061 GCTAAAAAGCACAAATAGANC_045512.2_19mer_win1_27782 27782 27800 859 CTATTTGTGCTTTTTAGCC 2062GGCTAAAAAGCACAAATAG NC_045512.2_19mer_win1_27783 27783 27801 860TATTTGTGCTTTTTAGCCT 2063 AGGCTAAAAAGCACAAATANC_045512.2_19mer_win1_27784 27784 27802 861 ATTTGTGCTTTTTAGCCTT 2064AAGGCTAAAAAGCACAAAT NC_045512.2_19mer_win1_27785 27785 27803 862TTTGTGCTTTTTAGCCTTT 2065 AAAGGCTAAAAAGCACAAANC_045512.2_19mer_win1_27786 27786 27804 863 TTGTGCTTTTTAGCCTTTC 2066GAAAGGCTAAAAAGCACAA NC_045512.2_19mer_win1_27787 27787 27805 864TGTGCTTTTTAGCCTTTCT 2067 AGAAAGGCTAAAAAGCACANC_045512.2_19mer_win1_27788 27788 27806 865 GTGCTTTTTAGCCTTTCTG 2068CAGAAAGGCTAAAAAGCAC NC_045512.2_19mer_win1_27789 27789 27807 866TGCTTTTTAGCCTTTCTGC 2069 GCAGAAAGGCTAAAAAGCANC_045512.2_19mer_win1_27790 27790 27808 867 GCTTTTTAGCCTTTCTGCT 2070AGCAGAAAGGCTAAAAAGC NC_045512.2_19mer_win1_27791 27791 27809 868CTTTTTAGCCTTTCTGCTA 2071 TAGCAGAAAGGCTAAAAAGNC_045512.2_19mer_win1_27792 27792 27810 869 TTTTTAGCCTTTCTGCTAT 2072ATAGCAGAAAGGCTAAAAA NC_045512.2_19mer_win1_27793 27793 27811 870TTTTAGCCTTTCTGCTATT 2073 AATAGCAGAAAGGCTAAAANC_045512.2_19mer_win1_27794 27794 27812 871 TTTAGCCTTTCTGCTATTC 2074GAATAGCAGAAAGGCTAAA NC_045512.2_19mer_win1_27795 27795 27813 872TTAGCCTTTCTGCTATTCC 2075 GGAATAGCAGAAAGGCTAANC_045512.2_19mer_win1_27796 27796 27814 873 TAGCCTTTCTGCTATTCCT 2076AGGAATAGCAGAAAGGCTA NC_045512.2_19mer_win1_27797 27797 27815 874AGCCTTTCTGCTATTCCTT 2077 AAGGAATAGCAGAAAGGCTNC_045512.2_19mer_win1_27798 27798 27816 875 GCCTTTCTGCTATTCCTTG 2078CAAGGAATAGCAGAAAGGC NC_045512.2_19mer_win1_27799 27799 27817 876CCTTTCTGCTATTCCTTGT 2079 ACAAGGAATAGCAGAAAGGNC_045512.2_19mer_win1_27800 27800 27818 877 CTTTCTGCTATTCCTTGTT 2080AACAAGGAATAGCAGAAAG NC_045512.2_19mer_win1_28270 28270 28288 878TAAAATGTCTGATAATGGA 2081 TCCATTATCAGACATTTTANC_045512.2_19mer_win1_28271 28271 28289 879 AAAATGTCTGATAATGGAC 2082GTCCATTATCAGACATTTT NC_045512.2_19mer_win1_28272 28272 28290 880AAATGTCTGATAATGGACC 2083 GGTCCATTATCAGACATTTNC_045512.2_19mer_win1_28273 28273 28291 881 AATGTCTGATAATGGACCC 2084GGGTCCATTATCAGACATT NC_045512.2_19mer_win1_28274 28274 28292 882ATGTCTGATAATGGACCCC 2085 GGGGTCCATTATCAGACATNC_045512.2_19mer_win1_28275 28275 28293 883 TGTCTGATAATGGACCCCA 2086TGGGGTCCATTATCAGACA NC_045512.2_19mer_win1_28276 28276 28294 884GTCTGATAATGGACCCCAA 2087 TTGGGGTCCATTATCAGACNC_045512.2_19mer_win1_28277 28277 28295 885 TCTGATAATGGACCCCAAA 2088TTTGGGGTCCATTATCAGA NC_045512.2_19mer_win1_28278 28278 28296 886CTGATAATGGACCCCAAAA 2089 TTTTGGGGTCCATTATCAGNC_045512.2_19mer_win1_28397 28397 28415 887 CCCCAAGGTTTACCCAATA 2090TATTGGGTAAACCTTGGGG NC_045512.2_19mer_win1_28398 28398 28416 888CCCAAGGTTTACCCAATAA 2091 TTATTGGGTAAACCTTGGGNC_045512.2_19mer_win1_28399 28399 28417 889 CCAAGGTTTACCCAATAAT 2092ATTATTGGGTAAACCTTGG NC_045512.2_19mer_win1_28400 28400 28418 890CAAGGTTTACCCAATAATA 2093 TATTATTGGGTAAACCTTGNC_045512.2_19mer_win1_28401 28401 28419 891 AAGGTTTACCCAATAATAC 2094GTATTATTGGGTAAACCTT NC_045512.2_19mer_win1_28402 28402 28420 892AGGTTTACCCAATAATACT 2095 AGTATTATTGGGTAAACCTNC_045512.2_19mer_win1_28403 28403 28421 893 GGTTTACCCAATAATACTG 2096CAGTATTATTGGGTAAACC NC_045512.2_19mer_win1_28404 28404 28422 894GTTTACCCAATAATACTGC 2097 GCAGTATTATTGGGTAAACNC_045512.2_19mer_win1_28405 28405 28423 895 TTTACCCAATAATACTGCG 2098CGCAGTATTATTGGGTAAA NC_045512.2_19mer_win1_28406 28406 28424 896TTACCCAATAATACTGCGT 2099 ACGCAGTATTATTGGGTAANC_045512.2_19mer_win1_28407 28407 28425 897 TACCCAATAATACTGCGTC 2100GACGCAGTATTATTGGGTA NC_045512.2_19mer_win1_28408 28408 28426 898ACCCAATAATACTGCGTCT 2101 AGACGCAGTATTATTGGGTNC_045512.2_19mer_win1_28409 28409 28427 899 CCCAATAATACTGCGTCTT 2102AAGACGCAGTATTATTGGG NC_045512.2_19mer_win1_28410 28410 28428 900CCAATAATACTGCGTCTTG 2103 CAAGACGCAGTATTATTGGNC_045512.2_19mer_win1_28411 28411 28429 901 CAATAATACTGCGTCTTGG 2104CCAAGACGCAGTATTATTG NC_045512.2_19mer_win1_28412 28412 28430 902AATAATACTGCGTCTTGGT 2105 ACCAAGACGCAGTATTATTNC_045512.2_19mer_win1_28413 28413 28431 903 ATAATACTGCGTCTTGGTT 2106AACCAAGACGCAGTATTAT NC_045512.2_19mer_win1_28414 28414 28432 904TAATACTGCGTCTTGGTTC 2107 GAACCAAGACGCAGTATTANC_045512.2_19mer_win1_28415 28415 28433 905 AATACTGCGTCTTGGTTCA 2108TGAACCAAGACGCAGTATT NC_045512.2_19mer_win1_28416 28416 28434 906ATACTGCGTCTTGGTTCAC 2109 GTGAACCAAGACGCAGTATNC_045512.2_19mer_win1_28513 28513 28531 907 AGATGACCAAATTGGCTAC 2110GTAGCCAATTTGGTCATCT NC_045512.2_19mer_win1_28514 28514 28532 908GATGACCAAATTGGCTACT 2111 AGTAGCCAATTTGGTCATCNC_045512.2_19mer_win1_28515 28515 28533 909 ATGACCAAATTGGCTACTA 2112TAGTAGCCAATTTGGTCAT NC_045512.2_19mer_win1_28516 28516 28534 910TGACCAAATTGGCTACTAC 2113 GTAGTAGCCAATTTGGTCANC_045512.2_19mer_win1_28517 28517 28535 911 GACCAAATTGGCTACTACC 2114GGTAGTAGCCAATTTGGTC NC_045512.2_19mer_win1_28518 28518 28536 912ACCAAATTGGCTACTACCG 2115 CGGTAGTAGCCAATTTGGTNC_045512.2_19mer_win1_28519 28519 28537 913 CCAAATTGGCTACTACCGA 2116TCGGTAGTAGCCAATTTGG NC_045512.2_19mer_win1_28520 28520 28538 914CAAATTGGCTACTACCGAA 2117 TTCGGTAGTAGCCAATTTGNC_045512.2_19mer_win1_28521 28521 28539 915 AAATTGGCTACTACCGAAG 2118CTTCGGTAGTAGCCAATTT NC_045512.2_19mer_win1_28522 28522 28540 916AATTGGCTACTACCGAAGA 2119 TCTTCGGTAGTAGCCAATTNC_045512.2_19mer_win1_28523 28523 28541 917 ATTGGCTACTACCGAAGAG 2120CTCTTCGGTAGTAGCCAAT NC_045512.2_19mer_win1_28524 28524 28542 918TTGGCTACTACCGAAGAGC 2121 GCTCTTCGGTAGTAGCCAANC_045512.2_19mer_win1_28525 28525 28543 919 TGGCTACTACCGAAGAGCT 2122AGCTCTTCGGTAGTAGCCA NC_045512.2_19mer_win1_28526 28526 28544 920GGCTACTACCGAAGAGCTA 2123 TAGCTCTTCGGTAGTAGCCNC_045512.2_19mer_win1_28527 28527 28545 921 GCTACTACCGAAGAGCTAC 2124GTAGCTCTTCGGTAGTAGC NC_045512.2_19mer_win1_28528 28528 28546 922CTACTACCGAAGAGCTACC 2125 GGTAGCTCTTCGGTAGTAGNC_045512.2_19mer_win1_28673 28673 28691 923 GCAACTGAGGGAGCCTTGA 2126TCAAGGCTCCCTCAGTTGC NC_045512.2_19mer_win1_28674 28674 28692 924CAACTGAGGGAGCCTTGAA 2127 TTCAAGGCTCCCTCAGTTGNC_045512.2_19mer_win1_28706 28706 28724 925 CACATTGGCACCCGCAATC 2128GATTGCGGGTGCCAATGTG NC_045512.2_19mer_win1_28707 28707 28725 926ACATTGGCACCCGCAATCC 2129 GGATTGCGGGTGCCAATGTNC_045512.2_19mer_win1_28708 28708 28726 927 CATTGGCACCCGCAATCCT 2130AGGATTGCGGGTGCCAATG NC_045512.2_19mer_win1_28744 28744 28762 928CGTGCTACAACTTCCTCAA 2131 TTGAGGAAGTTGTAGCACGNC_045512.2_19mer_win1_28745 28745 28763 929 GTGCTACAACTTCCTCAAG 2132CTTGAGGAAGTTGTAGCAC NC_045512.2_19mer_win1_28746 28746 28764 930TGCTACAACTTCCTCAAGG 2133 CCTTGAGGAAGTTGTAGCANC_045512.2_19mer_win1_28747 28747 28765 931 GCTACAACTTCCTCAAGGA 2134TCCTTGAGGAAGTTGTAGC NC_045512.2_19mer_win1_28748 28748 28766 932CTACAACTTCCTCAAGGAA 2135 TTCCTTGAGGAAGTTGTAGNC_045512.2_19mer_win1_28749 28749 28767 933 TACAACTTCCTCAAGGAAC 2136GTTCCTTGAGGAAGTTGTA NC_045512.2_19mer_win1_28750 28750 28768 934ACAACTTCCTCAAGGAACA 2137 TGTTCCTTGAGGAAGTTGTNC_045512.2_19mer_win1_28751 28751 28769 935 CAACTTCCTCAAGGAACAA 2138TTGTTCCTTGAGGAAGTTG NC_045512.2_19mer_win1_28752 28752 28770 936AACTTCCTCAAGGAACAAC 2139 GTTGTTCCTTGAGGAAGTTNC_045512.2_19mer_win1_28753 28753 28771 937 ACTTCCTCAAGGAACAACA 2140TGTTGTTCCTTGAGGAAGT NC_045512.2_19mer_win1_28754 28754 28772 938CTTCCTCAAGGAACAACAT 2141 ATGTTGTTCCTTGAGGAAGNC_045512.2_19mer_win1_28755 28755 28773 939 TTCCTCAAGGAACAACATT 2142AATGTTGTTCCTTGAGGAA NC_045512.2_19mer_win1_28756 28756 28774 940TCCTCAAGGAACAACATTG 2143 CAATGTTGTTCCTTGAGGANC_045512.2_19mer_win1_28757 28757 28775 941 CCTCAAGGAACAACATTGC 2144GCAATGTTGTTCCTTGAGG NC_045512.2_19mer_win1_28758 28758 28776 942CTCAAGGAACAACATTGCC 2145 GGCAATGTTGTTCCTTGAGNC_045512.2_19mer_win1_28759 28759 28777 943 TCAAGGAACAACATTGCCA 2146TGGCAATGTTGTTCCTTGA NC_045512.2_19mer_win1_28760 28760 28778 944CAAGGAACAACATTGCCAA 2147 TTGGCAATGTTGTTCCTTGNC_045512.2_19mer_win1_28761 28761 28779 945 AAGGAACAACATTGCCAAA 2148TTTGGCAATGTTGTTCCTT NC_045512.2_19mer_win1_28762 28762 28780 946AGGAACAACATTGCCAAAA 2149 TTTTGGCAATGTTGTTCCTNC_045512.2_19mer_win1_28763 28763 28781 947 GGAACAACATTGCCAAAAG 2150CTTTTGGCAATGTTGTTCC NC_045512.2_19mer_win1_28764 28764 28782 948GAACAACATTGCCAAAAGG 2151 CCTTTTGGCAATGTTGTTCNC_045512.2_19mer_win1_28765 28765 28783 949 AACAACATTGCCAAAAGGC 2152GCCTTTTGGCAATGTTGTT NC_045512.2_19mer_win1_28766 28766 28784 950ACAACATTGCCAAAAGGCT 2153 AGCCTTTTGGCAATGTTGTNC_045512.2_19mer_win1_28767 28767 28785 951 CAACATTGCCAAAAGGCTT 2154AAGCCTTTTGGCAATGTTG NC_045512.2_19mer_win1_28768 28768 28786 952AACATTGCCAAAAGGCTTC 2155 GAAGCCTTTTGGCAATGTTNC_045512.2_19mer_win1_28769 28769 28787 953 ACATTGCCAAAAGGCTTCT 2156AGAAGCCTTTTGGCAATGT NC_045512.2_19mer_win1_28770 28770 28788 954CATTGCCAAAAGGCTTCTA 2157 TAGAAGCCTTTTGGCAATGNC_045512.2_19mer_win1_28771 28771 28789 955 ATTGCCAAAAGGCTTCTAC 2158GTAGAAGCCTTTTGGCAAT NC_045512.2_19mer_win1_28772 28772 28790 956TTGCCAAAAGGCTTCTACG 2159 CGTAGAAGCCTTTTGGCAANC_045512.2_19mer_win1_28773 28773 28791 957 TGCCAAAAGGCTTCTACGC 2160GCGTAGAAGCCTTTTGGCA NC_045512.2_19mer_win1_28774 28774 28792 958GCCAAAAGGCTTCTACGCA 2161 TGCGTAGAAGCCTTTTGGCNC_045512.2_19mer_win1_28775 28775 28793 959 CCAAAAGGCTTCTACGCAG 2162CTGCGTAGAAGCCTTTTGG NC_045512.2_19mer_win1_28776 28776 28794 960CAAAAGGCTTCTACGCAGA 2163 TCTGCGTAGAAGCCTTTTGNC_045512.2_19mer_win1_28799 28799 28817 961 AGCAGAGGCGGCAGTCAAG 2164CTTGACTGCCGCCTCTGCT NC_045512.2_19mer_win1_28800 28800 28818 962GCAGAGGCGGCAGTCAAGC 2165 GCTTGACTGCCGCCTCTGCNC_045512.2_19mer_win1_28801 28801 28819 963 CAGAGGCGGCAGTCAAGCC 2166GGCTTGACTGCCGCCTCTG NC_045512.2_19mer_win1_28802 28802 28820 964AGAGGCGGCAGTCAAGCCT 2167 AGGCTTGACTGCCGCCTCTNC_045512.2_19mer_win1_28803 28803 28821 965 GAGGCGGCAGTCAAGCCTC 2168GAGGCTTGACTGCCGCCTC NC_045512.2_19mer_win1_28804 28804 28822 966AGGCGGCAGTCAAGCCTCT 2169 AGAGGCTTGACTGCCGCCTNC_045512.2_19mer_win1_28805 28805 28823 967 GGCGGCAGTCAAGCCTCTT 2170AAGAGGCTTGACTGCCGCC NC_045512.2_19mer_win1_28806 28806 28824 968GCGGCAGTCAAGCCTCTTC 2171 GAAGAGGCTTGACTGCCGCNC_045512.2_19mer_win1_28807 28807 28825 969 CGGCAGTCAAGCCTCTTCT 2172AGAAGAGGCTTGACTGCCG NC_045512.2_19mer_win1_28808 28808 28826 970GGCAGTCAAGCCTCTTCTC 2173 GAGAAGAGGCTTGACTGCCNC_045512.2_19mer_win1_28809 28809 28827 971 GCAGTCAAGCCTCTTCTCG 2174CGAGAAGAGGCTTGACTGC NC_045512.2_19mer_win1_28946 28946 28964 972GACAGATTGAACCAGCTTG 2175 CAAGCTGGTTCAATCTGTCNC_045512.2_19mer_win1_28947 28947 28965 973 ACAGATTGAACCAGCTTGA 2176TCAAGCTGGTTCAATCTGT NC_045512.2_19mer_win1_28948 28948 28966 974CAGATTGAACCAGCTTGAG 2177 CTCAAGCTGGTTCAATCTGNC_045512.2_19mer_win1_28949 28949 28967 975 AGATTGAACCAGCTTGAGA 2178TCTCAAGCTGGTTCAATCT NC_045512.2_19mer_win1_28950 28950 28968 976GATTGAACCAGCTTGAGAG 2179 CTCTCAAGCTGGTTCAATCNC_045512.2_19mer_win1_28951 28951 28969 977 ATTGAACCAGCTTGAGAGC 2180GCTCTCAAGCTGGTTCAAT NC_045512.2_19mer_win1_28952 28952 28970 978TTGAACCAGCTTGAGAGCA 2181 TGCTCTCAAGCTGGTTCAANC_045512.2_19mer_win1_28953 28953 28971 979 TGAACCAGCTTGAGAGCAA 2182TTGCTCTCAAGCTGGTTCA NC_045512.2_19mer_win1_28954 28954 28972 980GAACCAGCTTGAGAGCAAA 2183 TTTGCTCTCAAGCTGGTTCNC_045512.2_19mer_win1_28976 28976 28994 981 TCTGGTAAAGGCCAACAAC 2184GTTGTTGGCCTTTACCAGA NC_045512.2_19mer_win1_28977 28977 28995 982CTGGTAAAGGCCAACAACA 2185 TGTTGTTGGCCTTTACCAGNC_045512.2_19mer_win1_28978 28978 28996 983 TGGTAAAGGCCAACAACAA 2186TTGTTGTTGGCCTTTACCA NC_045512.2_19mer_win1_28979 28979 28997 984GGTAAAGGCCAACAACAAC 2187 GTTGTTGTTGGCCTTTACCNC_045512.2_19mer_win1_28980 28980 28998 985 GTAAAGGCCAACAACAACA 2188TGTTGTTGTTGGCCTTTAC NC_045512.2_19mer_win1_28981 28981 28999 986TAAAGGCCAACAACAACAA 2189 TTGTTGTTGTTGGCCTTTANC_045512.2_19mer_win1_28982 28982 29000 987 AAAGGCCAACAACAACAAG 2190CTTGTTGTTGTTGGCCTTT NC_045512.2_19mer_win1_28983 28983 29001 988AAGGCCAACAACAACAAGG 2191 CCTTGTTGTTGTTGGCCTTNC_045512.2_19mer_win1_28984 28984 29002 989 AGGCCAACAACAACAAGGC 2192GCCTTGTTGTTGTTGGCCT NC_045512.2_19mer_win1_28985 28985 29003 990GGCCAACAACAACAAGGCC 2193 GGCCTTGTTGTTGTTGGCCNC_045512.2_19mer_win1_28986 28986 29004 991 GCCAACAACAACAAGGCCA 2194TGGCCTTGTTGTTGTTGGC NC_045512.2_19mer_win1_28987 28987 29005 992CCAACAACAACAAGGCCAA 2195 TTGGCCTTGTTGTTGTTGGNC_045512.2_19mer_win1_28988 28988 29006 993 CAACAACAACAAGGCCAAA 2196TTTGGCCTTGTTGTTGTTG NC_045512.2_19mer_win1_28989 28989 29007 994AACAACAACAAGGCCAAAC 2197 GTTTGGCCTTGTTGTTGTTNC_045512.2_19mer_win1_28990 28990 29008 995 ACAACAACAAGGCCAAACT 2198AGTTTGGCCTTGTTGTTGT NC_045512.2_19mer_win1_28991 28991 29009 996CAACAACAAGGCCAAACTG 2199 CAGTTTGGCCTTGTTGTTGNC_045512.2_19mer_win1_28992 28992 29010 997 AACAACAAGGCCAAACTGT 2200ACAGTTTGGCCTTGTTGTT NC_045512.2_19mer_win1_28993 28993 29011 998ACAACAAGGCCAAACTGTC 2201 GACAGTTTGGCCTTGTTGTNC_045512.2_19mer_win1_28994 28994 29012 999 CAACAAGGCCAAACTGTCA 2202TGACAGTTTGGCCTTGTTG NC_045512.2_19mer_win1_28995 28995 29013 1000AACAAGGCCAAACTGTCAC 2203 GTGACAGTTTGGCCTTGTTNC_045512.2_19mer_win1_28996 28996 29014 1001 ACAAGGCCAAACTGTCACT 2204AGTGACAGTTTGGCCTTGT NC_045512.2_19mer_win1_28997 28997 29015 1002CAAGGCCAAACTGTCACTA 2205 TAGTGACAGTTTGGCCTTGNC_045512.2_19mer_win1_28998 28998 29016 1003 AAGGCCAAACTGTCACTAA 2206TTAGTGACAGTTTGGCCTT NC_045512.2_19mer_win1_28999 28999 29017 1004AGGCCAAACTGTCACTAAG 2207 CTTAGTGACAGTTTGGCCTNC_045512.2_19mer_win1_29000 29000 29018 1005 GGCCAAACTGTCACTAAGA 2208TCTTAGTGACAGTTTGGCC NC_045512.2_19mer_win1_29001 29001 29019 1006GCCAAACTGTCACTAAGAA 2209 TTCTTAGTGACAGTTTGGCNC_045512.2_19mer_win1_29002 29002 29020 1007 CCAAACTGTCACTAAGAAA 2210TTTCTTAGTGACAGTTTGG NC_045512.2_19mer_win1_29003 29003 29021 1008CAAACTGTCACTAAGAAAT 2211 ATTTCTTAGTGACAGTTTGNC_045512.2_19mer_win1_29004 29004 29022 1009 AAACTGTCACTAAGAAATC 2212GATTTCTTAGTGACAGTTT NC_045512.2_19mer_win1_29005 29005 29023 1010AACTGTCACTAAGAAATCT 2213 AGATTTCTTAGTGACAGTTNC_045512.2_19mer_win1_29006 29006 29024 1011 ACTGTCACTAAGAAATCTG 2214CAGATTTCTTAGTGACAGT NC_045512.2_19mer_win1_29007 29007 29025 1012CTGTCACTAAGAAATCTGC 2215 GCAGATTTCTTAGTGACAGNC_045512.2_19mer_win1_29008 29008 29026 1013 TGTCACTAAGAAATCTGCT 2216AGCAGATTTCTTAGTGACA NC_045512.2_19mer_win1_29009 29009 29027 1014GTCACTAAGAAATCTGCTG 2217 CAGCAGATTTCTTAGTGACNC_045512.2_19mer_win1_29010 29010 29028 1015 TCACTAAGAAATCTGCTGC 2218GCAGCAGATTTCTTAGTGA NC_045512.2_19mer_win1_29011 29011 29029 1016CACTAAGAAATCTGCTGCT 2219 AGCAGCAGATTTCTTAGTGNC_045512.2_19mer_win1_29012 29012 29030 1017 ACTAAGAAATCTGCTGCTG 2220CAGCAGCAGATTTCTTAGT NC_045512.2_19mer_win1_29013 29013 29031 1018CTAAGAAATCTGCTGCTGA 2221 TCAGCAGCAGATTTCTTAGNC_045512.2_19mer_win1_29014 29014 29032 1019 TAAGAAATCTGCTGCTGAG 2222CTCAGCAGCAGATTTCTTA NC_045512.2_19mer_win1_29015 29015 29033 1020AAGAAATCTGCTGCTGAGG 2223 CCTCAGCAGCAGATTTCTTNC_045512.2_19mer_win1_29016 29016 29034 1021 AGAAATCTGCTGCTGAGGC 2224GCCTCAGCAGCAGATTTCT NC_045512.2_19mer_win1_29144 29144 29162 1022CTAATCAGACAAGGAACTG 2225 CAGTTCCTTGTCTGATTAGNC_045512.2_19mer_win1_29145 29145 29163 1023 TAATCAGACAAGGAACTGA 2226TCAGTTCCTTGTCTGATTA NC_045512.2_19mer_win1_29146 29146 29164 1024AATCAGACAAGGAACTGAT 2227 ATCAGTTCCTTGTCTGATTNC_045512.2_19mer_win1_29147 29147 29165 1025 ATCAGACAAGGAACTGATT 2228AATCAGTTCCTTGTCTGAT NC_045512.2_19mer_win1_29148 29148 29166 1026TCAGACAAGGAACTGATTA 2229 TAATCAGTTCCTTGTCTGANC_045512.2_19mer_win1_29149 29149 29167 1027 CAGACAAGGAACTGATTAC 2230GTAATCAGTTCCTTGTCTG NC_045512.2_19mer_win1_29150 29150 29168 1028AGACAAGGAACTGATTACA 2231 TGTAATCAGTTCCTTGTCTNC_045512.2_19mer_win1_29151 29151 29169 1029 GACAAGGAACTGATTACAA 2232TTGTAATCAGTTCCTTGTC NC_045512.2_19mer_win1_29152 29152 29170 1030ACAAGGAACTGATTACAAA 2233 TTTGTAATCAGTTCCTTGTNC_045512.2_19mer_win1_29153 29153 29171 1031 CAAGGAACTGATTACAAAC 2234GTTTGTAATCAGTTCCTTG NC_045512.2_19mer_win1_29154 29154 29172 1032AAGGAACTGATTACAAACA 2235 TGTTTGTAATCAGTTCCTTNC_045512.2_19mer_win1_29174 29174 29192 1033 TGGCCGCAAATTGCACAAT 2236ATTGTGCAATTTGCGGCCA NC_045512.2_19mer_win1_29175 29175 29193 1034GGCCGCAAATTGCACAATT 2237 AATTGTGCAATTTGCGGCCNC_045512.2_19mer_win1_29176 29176 29194 1035 GCCGCAAATTGCACAATTT 2238AAATTGTGCAATTTGCGGC NC_045512.2_19mer_win1_29177 29177 29195 1036CCGCAAATTGCACAATTTG 2239 CAAATTGTGCAATTTGCGGNC_045512.2_19mer_win1_29178 29178 29196 1037 CGCAAATTGCACAATTTGC 2240GCAAATTGTGCAATTTGCG NC_045512.2_19mer_win1_29228 29228 29246 1038CGCATTGGCATGGAAGTCA 2241 TGACTTCCATGCCAATGCGNC_045512.2_19mer_win1_29229 29229 29247 1039 GCATTGGCATGGAAGTCAC 2242GTGACTTCCATGCCAATGC NC_045512.2_19mer_win1_29230 29230 29248 1040CATTGGCATGGAAGTCACA 2243 TGTGACTTCCATGCCAATGNC_045512.2_19mer_win1_29231 29231 29249 1041 ATTGGCATGGAAGTCACAC 2244GTGTGACTTCCATGCCAAT NC_045512.2_19mer_win1_29232 29232 29250 1042TTGGCATGGAAGTCACACC 2245 GGTGTGACTTCCATGCCAANC_045512.2_19mer_win1_29233 29233 29251 1043 TGGCATGGAAGTCACACCT 2246AGGTGTGACTTCCATGCCA NC_045512.2_19mer_win1_29234 29234 29252 1044GGCATGGAAGTCACACCTT 2247 AAGGTGTGACTTCCATGCCNC_045512.2_19mer_win1_29235 29235 29253 1045 GCATGGAAGTCACACCTTC 2248GAAGGTGTGACTTCCATGC NC_045512.2_19mer_win1_29236 29236 29254 1046CATGGAAGTCACACCTTCG 2249 CGAAGGTGTGACTTCCATGNC_045512.2_19mer_win1_29237 29237 29255 1047 ATGGAAGTCACACCTTCGG 2250CCGAAGGTGTGACTTCCAT NC_045512.2_19mer_win1_29238 29238 29256 1048TGGAAGTCACACCTTCGGG 2251 CCCGAAGGTGTGACTTCCANC_045512.2_19mer_win1_29239 29239 29257 1049 GGAAGTCACACCTTCGGGA 2252TCCCGAAGGTGTGACTTCC NC_045512.2_19mer_win1_29240 29240 29258 1050GAAGTCACACCTTCGGGAA 2253 TTCCCGAAGGTGTGACTTCNC_045512.2_19mer_win1_29241 29241 29259 1051 AAGTCACACCTTCGGGAAC 2254GTTCCCGAAGGTGTGACTT NC_045512.2_19mer_win1_29285 29285 29303 1052AAATTGGATGACAAAGATC 2255 GATCTTTGTCATCCAATTTNC_045512.2_19mer_win1_29286 29286 29304 1053 AATTGGATGACAAAGATCC 2256GGATCTTTGTCATCCAATT NC_045512.2_19mer_win1_29287 29287 29305 1054ATTGGATGACAAAGATCCA 2257 TGGATCTTTGTCATCCAATNC_045512.2_19mer_win1_29342 29342 29360 1055 ATTGACGCATACAAAACAT 2258ATGTTTTGTATGCGTCAAT NC_045512.2_19mer_win1_29343 29343 29361 1056TTGACGCATACAAAACATT 2259 AATGTTTTGTATGCGTCAANC_045512.2_19mer_win1_29344 29344 29362 1057 TGACGCATACAAAACATTC 2260GAATGTTTTGTATGCGTCA NC_045512.2_19mer_win1_29345 29345 29363 1058GACGCATACAAAACATTCC 2261 GGAATGTTTTGTATGCGTCNC_045512.2_19mer_win1_29346 29346 29364 1059 ACGCATACAAAACATTCCC 2262GGGAATGTTTTGTATGCGT NC_045512.2_19mer_win1_29347 29347 29365 1060CGCATACAAAACATTCCCA 2263 TGGGAATGTTTTGTATGCGNC_045512.2_19mer_win1_29348 29348 29366 1061 GCATACAAAACATTCCCAC 2264GTGGGAATGTTTTGTATGC NC_045512.2_19mer_win1_29349 29349 29367 1062CATACAAAACATTCCCACC 2265 GGTGGGAATGTTTTGTATGNC_045512.2_19mer_win1_29350 29350 29368 1063 ATACAAAACATTCCCACCA 2266TGGTGGGAATGTTTTGTAT NC_045512.2_19mer_win1_29351 29351 29369 1064TACAAAACATTCCCACCAA 2267 TTGGTGGGAATGTTTTGTANC_045512.2_19mer_win1_29352 29352 29370 1065 ACAAAACATTCCCACCAAC 2268GTTGGTGGGAATGTTTTGT NC_045512.2_19mer_win1_29353 29353 29371 1066CAAAACATTCCCACCAACA 2269 TGTTGGTGGGAATGTTTTGNC_045512.2_19mer_win1_29354 29354 29372 1067 AAAACATTCCCACCAACAG 2270CTGTTGGTGGGAATGTTTT NC_045512.2_19mer_win1_29355 29355 29373 1068AAACATTCCCACCAACAGA 2271 TCTGTTGGTGGGAATGTTTNC_045512.2_19mer_win1_29356 29356 29374 1069 AACATTCCCACCAACAGAG 2272CTCTGTTGGTGGGAATGTT NC_045512.2_19mer_win1_29357 29357 29375 1070ACATTCCCACCAACAGAGC 2273 GCTCTGTTGGTGGGAATGTNC_045512.2_19mer_win1_29358 29358 29376 1071 CATTCCCACCAACAGAGCC 2274GGCTCTGTTGGTGGGAATG NC_045512.2_19mer_win1_29359 29359 29377 1072ATTCCCACCAACAGAGCCT 2275 AGGCTCTGTTGGTGGGAATNC_045512.2_19mer_win1_29360 29360 29378 1073 TTCCCACCAACAGAGCCTA 2276TAGGCTCTGTTGGTGGGAA NC_045512.2_19mer_win1_29361 29361 29379 1074TCCCACCAACAGAGCCTAA 2277 TTAGGCTCTGTTGGTGGGANC_045512.2_19mer_win1_29362 29362 29380 1075 CCCACCAACAGAGCCTAAA 2278TTTAGGCTCTGTTGGTGGG NC_045512.2_19mer_win1_29363 29363 29381 1076CCACCAACAGAGCCTAAAA 2279 TTTTAGGCTCTGTTGGTGGNC_045512.2_19mer_win1_29364 29364 29382 1077 CACCAACAGAGCCTAAAAA 2280TTTTTAGGCTCTGTTGGTG NC_045512.2_19mer_win1_29365 29365 29383 1078ACCAACAGAGCCTAAAAAG 2281 CTTTTTAGGCTCTGTTGGTNC_045512.2_19mer_win1_29366 29366 29384 1079 CCAACAGAGCCTAAAAAGG 2282CCTTTTTAGGCTCTGTTGG NC_045512.2_19mer_win1_29367 29367 29385 1080CAACAGAGCCTAAAAAGGA 2283 TCCTTTTTAGGCTCTGTTGNC_045512.2_19mer_win1_29368 29368 29386 1081 AACAGAGCCTAAAAAGGAC 2284GTCCTTTTTAGGCTCTGTT NC_045512.2_19mer_win1_29369 29369 29387 1082ACAGAGCCTAAAAAGGACA 2285 TGTCCTTTTTAGGCTCTGTNC_045512.2_19mer_win1_29370 29370 29388 1083 CAGAGCCTAAAAAGGACAA 2286TTGTCCTTTTTAGGCTCTG NC_045512.2_19mer_win1_29371 29371 29389 1084AGAGCCTAAAAAGGACAAA 2287 TTTGTCCTTTTTAGGCTCTNC_045512.2_19mer_win1_29372 29372 29390 1085 GAGCCTAAAAAGGACAAAA 2288TTTTGTCCTTTTTAGGCTC NC_045512.2_19mer_win1_29373 29373 29391 1086AGCCTAAAAAGGACAAAAA 2289 TTTTTGTCCTTTTTAGGCTNC_045512.2_19mer_win1_29374 29374 29392 1087 GCCTAAAAAGGACAAAAAG 2290CTTTTTGTCCTTTTTAGGC NC_045512.2_19mer_win1_29375 29375 29393 1088CCTAAAAAGGACAAAAAGA 2291 TCTTTTTGTCCTTTTTAGGNC_045512.2_19mer_win1_29376 29376 29394 1089 CTAAAAAGGACAAAAAGAA 2292TTCTTTTTGTCCTTTTTAG NC_045512.2_19mer_win1_29444 29444 29462 1090ACTGTGACTCTTCTTCCTG 2293 CAGGAAGAAGAGTCACAGTNC_045512.2_19mer_win1_29445 29445 29463 1091 CTGTGACTCTTCTTCCTGC 2294GCAGGAAGAAGAGTCACAG NC_045512.2_19mer_win1_29543 29543 29561 1092GACCACACAAGGCAGATGG 2295 CCATCTGCCTTGTGTGGTCNC_045512.2_19mer_win1_29544 29544 29562 1093 ACCACACAAGGCAGATGGG 2296CCCATCTGCCTTGTGTGGT NC_045512.2_19mer_win1_29545 29545 29563 1094CCACACAAGGCAGATGGGC 2297 GCCCATCTGCCTTGTGTGGNC_045512.2_19mer_win1_29546 29546 29564 1095 CACACAAGGCAGATGGGCT 2298AGCCCATCTGCCTTGTGTG NC_045512.2_19mer_win1_29547 29547 29565 1096ACACAAGGCAGATGGGCTA 2299 TAGCCCATCTGCCTTGTGTNC_045512.2_19mer_win1_29548 29548 29566 1097 CACAAGGCAGATGGGCTAT 2300ATAGCCCATCTGCCTTGTG NC_045512.2_19mer_win1_29598 29598 29616 1098ATAGTCTACTCTTGTGCAG 2301 CTGCACAAGAGTAGACTATNC_045512.2_19mer_win1_29599 29599 29617 1099 TAGTCTACTCTTGTGCAGA 2302TCTGCACAAGAGTAGACTA NC_045512.2_19mer_win1_29600 29600 29618 1100AGTCTACTCTTGTGCAGAA 2303 TTCTGCACAAGAGTAGACTNC_045512.2_19mer_win1_29601 29601 29619 1101 GTCTACTCTTGTGCAGAAT 2304ATTCTGCACAAGAGTAGAC NC_045512.2_19mer_win1_29602 29602 29620 1102TCTACTCTTGTGCAGAATG 2305 CATTCTGCACAAGAGTAGANC_045512.2_19mer_win1_29603 29603 29621 1103 CTACTCTTGTGCAGAATGA 2306TCATTCTGCACAAGAGTAG NC_045512.2_19mer_win1_29604 29604 29622 1104TACTCTTGTGCAGAATGAA 2307 TTCATTCTGCACAAGAGTANC_045512.2_19mer_win1_29605 29605 29623 1105 ACTCTTGTGCAGAATGAAT 2308ATTCATTCTGCACAAGAGT NC_045512.2_19mer_win1_29606 29606 29624 1106CTCTTGTGCAGAATGAATT 2309 AATTCATTCTGCACAAGAGNC_045512.2_19mer_win1_29607 29607 29625 1107 TCTTGTGCAGAATGAATTC 2310GAATTCATTCTGCACAAGA NC_045512.2_19mer_win1_29608 29608 29626 1108CTTGTGCAGAATGAATTCT 2311 AGAATTCATTCTGCACAAGNC_045512.2_19mer_win1_29609 29609 29627 1109 TTGTGCAGAATGAATTCTC 2312GAGAATTCATTCTGCACAA NC_045512.2_19mer_win1_29610 29610 29628 1110TGTGCAGAATGAATTCTCG 2313 CGAGAATTCATTCTGCACANC_045512.2_19mer_win1_29611 29611 29629 1111 GTGCAGAATGAATTCTCGT 2314ACGAGAATTCATTCTGCAC NC_045512.2_19mer_win1_29612 29612 29630 1112TGCAGAATGAATTCTCGTA 2315 TACGAGAATTCATTCTGCANC_045512.2_19mer_win1_29652 29652 29670 1113 TAGTTAACTTTAATCTCAC 2316GTGAGATTAAAGTTAACTA NC_045512.2_19mer_win1_29653 29653 29671 1114AGTTAACTTTAATCTCACA 2317 TGTGAGATTAAAGTTAACTNC_045512.2_19mer_win1_29654 29654 29672 1115 GTTAACTTTAATCTCACAT 2318ATGTGAGATTAAAGTTAAC NC_045512.2_19mer_win1_29655 29655 29673 1116TTAACTTTAATCTCACATA 2319 TATGTGAGATTAAAGTTAANC_045512.2_19mer_win1_29656 29656 29674 1117 TAACTTTAATCTCACATAG 2320CTATGTGAGATTAAAGTTA NC_045512.2_19mer_win1_29657 29657 29675 1118AACTTTAATCTCACATAGC 2321 GCTATGTGAGATTAAAGTTNC_045512.2_19mer_win1_29658 29658 29676 1119 ACTTTAATCTCACATAGCA 2322TGCTATGTGAGATTAAAGT NC_045512.2_19mer_win1_29659 29659 29677 1120CTTTAATCTCACATAGCAA 2323 TTGCTATGTGAGATTAAAGNC_045512.2_19mer_win1_29660 29660 29678 1121 TTTAATCTCACATAGCAAT 2324ATTGCTATGTGAGATTAAA NC_045512.2_19mer_win1_29661 29661 29679 1122TTAATCTCACATAGCAATC 2325 GATTGCTATGTGAGATTAANC_045512.2_19mer_win1_29662 29662 29680 1123 TAATCTCACATAGCAATCT 2326AGATTGCTATGTGAGATTA NC_045512.2_19mer_win1_29663 29663 29681 1124AATCTCACATAGCAATCTT 2327 AAGATTGCTATGTGAGATTNC_045512.2_19mer_win1_29664 29664 29682 1125 ATCTCACATAGCAATCTTT 2328AAAGATTGCTATGTGAGAT NC_045512.2_19mer_win1_29665 29665 29683 1126TCTCACATAGCAATCTTTA 2329 TAAAGATTGCTATGTGAGANC_045512.2_19mer_win1_29666 29666 29684 1127 CTCACATAGCAATCTTTAA 2330TTAAAGATTGCTATGTGAG NC_045512.2_19mer_win1_29667 29667 29685 1128TCACATAGCAATCTTTAAT 2331 ATTAAAGATTGCTATGTGANC_045512.2_19mer_win1_29668 29668 29686 1129 CACATAGCAATCTTTAATC 2332GATTAAAGATTGCTATGTG NC_045512.2_19mer_win1_29669 29669 29687 1130ACATAGCAATCTTTAATCA 2333 TGATTAAAGATTGCTATGTNC_045512.2_19mer_win1_29689 29689 29707 1131 TGTGTAACATTAGGGAGGA 2334TCCTCCCTAATGTTACACA NC_045512.2_19mer_win1_29690 29690 29708 1132GTGTAACATTAGGGAGGAC 2335 GTCCTCCCTAATGTTACACNC_045512.2_19mer_win1_29691 29691 29709 1133 TGTAACATTAGGGAGGACT 2336AGTCCTCCCTAATGTTACA NC_045512.2_19mer_win1_29692 29692 29710 1134GTAACATTAGGGAGGACTT 2337 AAGTCCTCCCTAATGTTACNC_045512.2_19mer_win1_29693 29693 29711 1135 TAACATTAGGGAGGACTTG 2338CAAGTCCTCCCTAATGTTA NC_045512.2_19mer_win1_29694 29694 29712 1136AACATTAGGGAGGACTTGA 2339 TCAAGTCCTCCCTAATGTTNC_045512.2_19mer_win1_29695 29695 29713 1137 ACATTAGGGAGGACTTGAA 2340TTCAAGTCCTCCCTAATGT NC_045512.2_19mer_win1_29696 29696 29714 1138CATTAGGGAGGACTTGAAA 2341 TTTCAAGTCCTCCCTAATGNC_045512.2_19mer_win1_29697 29697 29715 1139 ATTAGGGAGGACTTGAAAG 2342CTTTCAAGTCCTCCCTAAT NC_045512.2_19mer_win1_29698 29698 29716 1140TTAGGGAGGACTTGAAAGA 2343 TCTTTCAAGTCCTCCCTAANC_045512.2_19mer_win1_29699 29699 29717 1141 TAGGGAGGACTTGAAAGAG 2344CTCTTTCAAGTCCTCCCTA NC_045512.2_19mer_win1_29700 29700 29718 1142AGGGAGGACTTGAAAGAGC 2345 GCTCTTTCAAGTCCTCCCTNC_045512.2_19mer_win1_29701 29701 29719 1143 GGGAGGACTTGAAAGAGCC 2346GGCTCTTTCAAGTCCTCCC NC_045512.2_19mer_win1_29702 29702 29720 1144GGAGGACTTGAAAGAGCCA 2347 TGGCTCTTTCAAGTCCTCCNC_045512.2_19mer_win1_29703 29703 29721 1145 GAGGACTTGAAAGAGCCAC 2348GTGGCTCTTTCAAGTCCTC NC_045512.2_19mer_win1_29704 29704 29722 1146AGGACTTGAAAGAGCCACC 2349 GGTGGCTCTTTCAAGTCCTNC_045512.2_19mer_win1_29705 29705 29723 1147 GGACTTGAAAGAGCCACCA 2350TGGTGGCTCTTTCAAGTCC NC_045512.2_19mer_win1_29706 29706 29724 1148GACTTGAAAGAGCCACCAC 2351 GTGGTGGCTCTTTCAAGTCNC_045512.2_19mer_win1_29707 29707 29725 1149 ACTTGAAAGAGCCACCACA 2352TGTGGTGGCTCTTTCAAGT NC_045512.2_19mer_win1_29708 29708 29726 1150CTTGAAAGAGCCACCACAT 2353 ATGTGGTGGCTCTTTCAAGNC_045512.2_19mer_win1_29709 29709 29727 1151 TTGAAAGAGCCACCACATT 2354AATGTGGTGGCTCTTTCAA NC_045512.2_19mer_win1_29710 29710 29728 1152TGAAAGAGCCACCACATTT 2355 AAATGTGGTGGCTCTTTCANC_045512.2_19mer_win1_29711 29711 29729 1153 GAAAGAGCCACCACATTTT 2356AAAATGTGGTGGCTCTTTC NC_045512.2_19mer_win1_29712 29712 29730 1154AAAGAGCCACCACATTTTC 2357 GAAAATGTGGTGGCTCTTTNC_045512.2_19mer_win1_29713 29713 29731 1155 AAGAGCCACCACATTTTCA 2358TGAAAATGTGGTGGCTCTT NC_045512.2_19mer_win1_29733 29733 29751 1156CGAGGCCACGCGGAGTACG 2359 CGTACTCCGCGTGGCCTCGNC_045512.2_19mer_win1_29734 29734 29752 1157 GAGGCCACGCGGAGTACGA 2360TCGTACTCCGCGTGGCCTC NC_045512.2_19mer_win1_29735 29735 29753 1158AGGCCACGCGGAGTACGAT 2361 ATCGTACTCCGCGTGGCCTNC_045512.2_19mer_win1_29736 29736 29754 1159 GGCCACGCGGAGTACGATC 2362GATCGTACTCCGCGTGGCC NC_045512.2_19mer_win1_29737 29737 29755 1160GCCACGCGGAGTACGATCG 2363 CGATCGTACTCCGCGTGGCNC_045512.2_19mer_win1_29738 29738 29756 1161 CCACGCGGAGTACGATCGA 2364TCGATCGTACTCCGCGTGG NC_045512.2_19mer_win1_29739 29739 29757 1162CACGCGGAGTACGATCGAG 2365 CTCGATCGTACTCCGCGTGNC_045512.2_19mer_win1_29770 29770 29788 1163 AATGCTAGGGAGAGCTGCC 2366GGCAGCTCTCCCTAGCATT NC_045512.2_19mer_win1_29771 29771 29789 1164ATGCTAGGGAGAGCTGCCT 2367 AGGCAGCTCTCCCTAGCATNC_045512.2_19mer_win1_29772 29772 29790 1165 TGCTAGGGAGAGCTGCCTA 2368TAGGCAGCTCTCCCTAGCA NC_045512.2_19mer_win1_29773 29773 29791 1166GCTAGGGAGAGCTGCCTAT 2369 ATAGGCAGCTCTCCCTAGCNC_045512.2_19mer_win1_29774 29774 29792 1167 CTAGGGAGAGCTGCCTATA 2370TATAGGCAGCTCTCCCTAG NC_045512.2_19mer_win1_29775 29775 29793 1168TAGGGAGAGCTGCCTATAT 2371 ATATAGGCAGCTCTCCCTANC_045512.2_19mer_win1_29776 29776 29794 1169 AGGGAGAGCTGCCTATATG 2372CATATAGGCAGCTCTCCCT NC_045512.2_19mer_win1_29777 29777 29795 1170GGGAGAGCTGCCTATATGG 2373 CCATATAGGCAGCTCTCCCNC_045512.2_19mer_win1_29778 29778 29796 1171 GGAGAGCTGCCTATATGGA 2374TCCATATAGGCAGCTCTCC NC_045512.2_19mer_win1_29779 29779 29797 1172GAGAGCTGCCTATATGGAA 2375 TTCCATATAGGCAGCTCTCNC_045512.2_19mer_win1_29780 29780 29798 1173 AGAGCTGCCTATATGGAAG 2376CTTCCATATAGGCAGCTCT NC_045512.2_19mer_win1_29781 29781 29799 1174GAGCTGCCTATATGGAAGA 2377 TCTTCCATATAGGCAGCTCNC_045512.2_19mer_win1_29782 29782 29800 1175 AGCTGCCTATATGGAAGAG 2378CTCTTCCATATAGGCAGCT NC_045512.2_19mer_win1_29783 29783 29801 1176GCTGCCTATATGGAAGAGC 2379 GCTCTTCCATATAGGCAGCNC_045512.2_19mer_win1_29784 29784 29802 1177 CTGCCTATATGGAAGAGCC 2380GGCTCTTCCATATAGGCAG NC_045512.2_19mer_win1_29785 29785 29803 1178TGCCTATATGGAAGAGCCC 2381 GGGCTCTTCCATATAGGCANC_045512.2_19mer_win1_29786 29786 29804 1179 GCCTATATGGAAGAGCCCT 2382AGGGCTCTTCCATATAGGC NC_045512.2_19mer_win1_29787 29787 29805 1180CCTATATGGAAGAGCCCTA 2383 TAGGGCTCTTCCATATAGGNC_045512.2_19mer_win1_29788 29788 29806 1181 CTATATGGAAGAGCCCTAA 2384TTAGGGCTCTTCCATATAG NC_045512.2_19mer_win1_29789 29789 29807 1182TATATGGAAGAGCCCTAAT 2385 ATTAGGGCTCTTCCATATANC_045512.2_19mer_win1_29790 29790 29808 1183 ATATGGAAGAGCCCTAATG 2386CATTAGGGCTCTTCCATAT NC_045512.2_19mer_win1_29791 29791 29809 1184TATGGAAGAGCCCTAATGT 2387 ACATTAGGGCTCTTCCATANC_045512.2_19mer_win1_29792 29792 29810 1185 ATGGAAGAGCCCTAATGTG 2388CACATTAGGGCTCTTCCAT NC_045512.2_19mer_win1_29793 29793 29811 1186TGGAAGAGCCCTAATGTGT 2389 ACACATTAGGGCTCTTCCANC_045512.2_19mer_win1_29794 29794 29812 1187 GGAAGAGCCCTAATGTGTA 2390TACACATTAGGGCTCTTCC NC_045512.2_19mer_win1_29795 29795 29813 1188GAAGAGCCCTAATGTGTAA 2391 TTACACATTAGGGCTCTTCNC_045512.2_19mer_win1_29796 29796 29814 1189 AAGAGCCCTAATGTGTAAA 2392TTTACACATTAGGGCTCTT NC_045512.2_19mer_win1_29797 29797 29815 1190AGAGCCCTAATGTGTAAAA 2393 TTTTACACATTAGGGCTCTNC_045512.2_19mer_win1_29798 29798 29816 1191 GAGCCCTAATGTGTAAAAT 2394ATTTTACACATTAGGGCTC NC_045512.2_19mer_win1_29799 29799 29817 1192AGCCCTAATGTGTAAAATT 2395 AATTTTACACATTAGGGCTNC_045512.2_19mer_win1_29800 29800 29818 1193 GCCCTAATGTGTAAAATTA 2396TAATTTTACACATTAGGGC NC_045512.2_19mer_win1_29801 29801 29819 1194CCCTAATGTGTAAAATTAA 2397 TTAATTTTACACATTAGGGNC_045512.2_19mer_win1_29802 29802 29820 1195 CCTAATGTGTAAAATTAAT 2398ATTAATTTTACACATTAGG NC_045512.2_19mer_win1_29803 29803 29821 1196CTAATGTGTAAAATTAATT 2399 AATTAATTTTACACATTAGNC_045512.2_19mer_win1_29804 29804 29822 1197 TAATGTGTAAAATTAATTT 2400AAATTAATTTTACACATTA NC_045512.2_19mer_win1_29805 29805 29823 1198AATGTGTAAAATTAATTTT 2401 AAAATTAATTTTACACATTNC_045512.2_19mer_win1_29806 29806 29824 1199 ATGTGTAAAATTAATTTTA 2402TAAAATTAATTTTACACAT NC_045512.2_19mer_win1_29807 29807 29825 1200TGTGTAAAATTAATTTTAG 2403 CTAAAATTAATTTTACACANC_045512.2_19mer_win1_29808 29808 29826 1201 GTGTAAAATTAATTTTAGT 2404ACTAAAATTAATTTTACAC NC_045512.2_19mer_win1_29809 29809 29827 1202TGTAAAATTAATTTTAGTA 2405 TACTAAAATTAATTTTACANC_045512.2_19mer_win1_29810 29810 29828 1203 GTAAAATTAATTTTAGTAG 2406CTACTAAAATTAATTTTAC 21-mer Target Sequences NC_045512.2_21mer_win1_00190190 210 2411 GACGAATGCCAAAGCAGGCAC 3393 CACGGACGAAACCGTAAGCAGNC_045512.2_21mer_win1_00191 191 211 2412 ACGAATGCCAAAGCAGGCACA 3394ACACGGACGAAACCGTAAGCA NC_045512.2_21mer_win1_00192 192 212 2413CGAATGCCAAAGCAGGCACAA 3395 AACACGGACGAAACCGTAAGCNC_045512.2_21mer_win1_00193 193 213 2414 GAATGCCAAAGCAGGCACAAC 3396CAACACGGACGAAACCGTAAG NC_045512.2_21mer_win1_00194 194 214 2415AATGCCAAAGCAGGCACAACG 3397 GCAACACGGACGAAACCGTAANC_045512.2_21mer_win1_00195 195 215 2416 ATGCCAAAGCAGGCACAACGT 3398TGCAACACGGACGAAACCGTA NC_045512.2_21mer_win1_00196 196 216 2417TGCCAAAGCAGGCACAACGTC 3399 CTGCAACACGGACGAAACCGTNC_045512.2_21mer_win1_00233 233 253 2418 GATCCAAAGCAGGCCCACACT 3400TCACACCCGGACGAAACCTAG NC_045512.2_21mer_win1_00234 234 254 2419ATCCAAAGCAGGCCCACACTG 3401 GTCACACCCGGACGAAACCTANC_045512.2_21mer_win1_00235 235 255 2420 TCCAAAGCAGGCCCACACTGG 3402GGTCACACCCGGACGAAACCT NC_045512.2_21mer_win1_00236 236 256 2421CCAAAGCAGGCCCACACTGGC 3403 CGGTCACACCCGGACGAAACCNC_045512.2_21mer_win1_00237 237 257 2422 CAAAGCAGGCCCACACTGGCT 3404TCGGTCACACCCGGACGAAAC NC_045512.2_21mer_win1_00238 238 258 2423AAAGCAGGCCCACACTGGCTT 3405 TTCGGTCACACCCGGACGAAANC_045512.2_21mer_win1_00239 239 259 2424 AAGCAGGCCCACACTGGCTTT 3406TTTCGGTCACACCCGGACGAA NC_045512.2_21mer_win1_00240 240 260 2425AGCAGGCCCACACTGGCTTTC 3407 CTTTCGGTCACACCCGGACGANC_045512.2_21mer_win1_00241 241 261 2426 GCAGGCCCACACTGGCTTTCC 3408CCTTTCGGTCACACCCGGACG NC_045512.2_21mer_win1_00242 242 262 2427CAGGCCCACACTGGCTTTCCA 3409 ACCTTTCGGTCACACCCGGACNC_045512.2_21mer_win1_00243 243 263 2428 AGGCCCACACTGGCTTTCCAT 3410TACCTTTCGGTCACACCCGGA NC_045512.2_21mer_win1_00244 244 264 2429GGCCCACACTGGCTTTCCATT 3411 TTACCTTTCGGTCACACCCGGNC_045512.2_21mer_win1_00245 245 265 2430 GCCCACACTGGCTTTCCATTC 3412CTTACCTTTCGGTCACACCCG NC_045512.2_21mer_win1_00246 246 266 2431CCCACACTGGCTTTCCATTCT 3413 TCTTACCTTTCGGTCACACCCNC_045512.2_21mer_win1_00247 247 267 2432 CCACACTGGCTTTCCATTCTA 3414ATCTTACCTTTCGGTCACACC NC_045512.2_21mer_win1_00248 248 268 2433CACACTGGCTTTCCATTCTAC 3415 CATCTTACCTTTCGGTCACACNC_045512.2_21mer_win1_00249 249 269 2434 ACACTGGCTTTCCATTCTACC 3416CCATCTTACCTTTCGGTCACA NC_045512.2_21mer_win1_00250 250 270 2435CACTGGCTTTCCATTCTACCT 3417 TCCATCTTACCTTTCGGTCACNC_045512.2_21mer_win1_00251 251 271 2436 ACTGGCTTTCCATTCTACCTC 3418CTCCATCTTACCTTTCGGTCA NC_045512.2_21mer_win1_00252 252 272 2437CTGGCTTTCCATTCTACCTCT 3419 TCTCCATCTTACCTTTCGGTCNC_045512.2_21mer_win1_00253 253 273 2438 TGGCTTTCCATTCTACCTCTC 3420CTCTCCATCTTACCTTTCGGT NC_045512.2_21mer_win1_00254 254 274 2439GGCTTTCCATTCTACCTCTCG 3421 GCTCTCCATCTTACCTTTCGGNC_045512.2_21mer_win1_00255 255 275 2440 GCTTTCCATTCTACCTCTCGG 3422GGCTCTCCATCTTACCTTTCG NC_045512.2_21mer_win1_00256 256 276 2441CTTTCCATTCTACCTCTCGGA 3423 AGGCTCTCCATCTTACCTTTCNC_045512.2_21mer_win1_00257 257 277 2442 TTTCCATTCTACCTCTCGGAA 3424AAGGCTCTCCATCTTACCTTT NC_045512.2_21mer_win1_00258 258 278 2443TTCCATTCTACCTCTCGGAAC 3425 CAAGGCTCTCCATCTTACCTTNC_045512.2_21mer_win1_00259 259 279 2444 TCCATTCTACCTCTCGGAACA 3426ACAAGGCTCTCCATCTTACCT NC_045512.2_21mer_win1_00288 288 308 2445AGTTGCTCTTTTGTGTGCAGG 3427 GGACGTGTGTTTTCTCGTTGANC_045512.2_21mer_win1_00289 289 309 2446 GTTGCTCTTTTGTGTGCAGGT 3428TGGACGTGTGTTTTCTCGTTG NC_045512.2_21mer_win1_00290 290 310 2447TTGCTCTTTTGTGTGCAGGTT 3429 TTGGACGTGTGTTTTCTCGTTNC_045512.2_21mer_win1_00291 291 311 2448 TGCTCTTTTGTGTGCAGGTTG 3430GTTGGACGTGTGTTTTCTCGT NC_045512.2_21mer_win1_00292 292 312 2449GCTCTTTTGTGTGCAGGTTGA 3431 AGTTGGACGTGTGTTTTCTCGNC_045512.2_21mer_win1_00293 293 313 2450 CTCTTTTGTGTGCAGGTTGAG 3432GAGTTGGACGTGTGTTTTCTC NC_045512.2_21mer_win1_00294 294 314 2451TCTTTTGTGTGCAGGTTGAGT 3433 TGAGTTGGACGTGTGTTTTCTNC_045512.2_21mer_win1_00295 295 315 2452 CTTTTGTGTGCAGGTTGAGTC 3434CTGAGTTGGACGTGTGTTTTC NC_045512.2_21mer_win1_00296 296 316 2453TTTTGTGTGCAGGTTGAGTCA 3435 ACTGAGTTGGACGTGTGTTTTNC_045512.2_21mer_win1_00297 297 317 2454 TTTGTGTGCAGGTTGAGTCAA 3436AACTGAGTTGGACGTGTGTTT NC_045512.2_21mer_win1_00298 298 318 2455TTGTGTGCAGGTTGAGTCAAA 3437 AAACTGAGTTGGACGTGTGTTNC_045512.2_21mer_win1_00299 299 319 2456 TGTGTGCAGGTTGAGTCAAAC 3438CAAACTGAGTTGGACGTGTGT NC_045512.2_21mer_win1_00300 300 320 2457GTGTGCAGGTTGAGTCAAACG 3439 GCAAACTGAGTTGGACGTGTGNC_045512.2_21mer_win1_00301 301 321 2458 TGTGCAGGTTGAGTCAAACGG 3440GGCAAACTGAGTTGGACGTGT NC_045512.2_21mer_win1_00302 302 322 2459GTGCAGGTTGAGTCAAACGGA 3441 AGGCAAACTGAGTTGGACGTGNC_045512.2_21mer_win1_00303 303 323 2460 TGCAGGTTGAGTCAAACGGAC 3442CAGGCAAACTGAGTTGGACGT NC_045512.2_21mer_win1_00304 304 324 2461GCAGGTTGAGTCAAACGGACA 3443 ACAGGCAAACTGAGTTGGACGNC_045512.2_21mer_win1_00455 455 475 2462 GAACTTGTCGGGATACACAAG 3444GAACACATAGGGCTGTTCAAG NC_045512.2_21mer_win1_00456 456 476 2463AACTTGTCGGGATACACAAGT 3445 TGAACACATAGGGCTGTTCAANC_045512.2_21mer_win1_00457 457 477 2464 ACTTGTCGGGATACACAAGTA 3446ATGAACACATAGGGCTGTTCA NC_045512.2_21mer_win1_00626 626 646 2465CAAGAAGAAGCATTCTTGCCA 3447 ACCGTTCTTACGAAGAAGAACNC_045512.2_21mer_win1_00627 627 647 2466 AAGAAGAAGCATTCTTGCCAT 3448TACCGTTCTTACGAAGAAGAA NC_045512.2_21mer_win1_00628 628 648 2467AGAAGAAGCATTCTTGCCATT 3449 TTACCGTTCTTACGAAGAAGANC_045512.2_21mer_win1_00629 629 649 2468 GAAGAAGCATTCTTGCCATTA 3450ATTACCGTTCTTACGAAGAAG NC_045512.2_21mer_win1_00630 630 650 2469AAGAAGCATTCTTGCCATTAT 3451 TATTACCGTTCTTACGAAGAANC_045512.2_21mer_win1_00631 631 651 2470 AGAAGCATTCTTGCCATTATT 3452TTATTACCGTTCTTACGAAGA NC_045512.2_21mer_win1_03352 3352 3372 2471ACCAATAAATTTTGAATGACT 3453 TCAGTAAGTTTTAAATAACCANC_045512.2_21mer_win1_03353 3353 3373 2472 CCAATAAATTTTGAATGACTG 3454GTCAGTAAGTTTTAAATAACC NC_045512.2_21mer_win1_03354 3354 3374 2473CAATAAATTTTGAATGACTGT 3455 TGTCAGTAAGTTTTAAATAACNC_045512.2_21mer_win1_03355 3355 3375 2474 AATAAATTTTGAATGACTGTT 3456TTGTCAGTAAGTTTTAAATAA NC_045512.2_21mer_win1_03356 3356 3376 2475ATAAATTTTGAATGACTGTTA 3457 ATTGTCAGTAAGTTTTAAATANC_045512.2_21mer_win1_03357 3357 3377 2476 TAAATTTTGAATGACTGTTAC 3458CATTGTCAGTAAGTTTTAAAT NC_045512.2_21mer_win1_03358 3358 3378 2477AAATTTTGAATGACTGTTACA 3459 ACATTGTCAGTAAGTTTTAAANC_045512.2_21mer_win1_06406 6406 6426 2478 GAGACTTCTTCATCACCTTTT 3460TTTTCCACTACTTCTTCAGAG NC_045512.2_21mer_win1_06407 6407 6427 2479AGACTTCTTCATCACCTTTTA 3461 ATTTTCCACTACTTCTTCAGANC_045512.2_21mer_win1_06408 6408 6428 2480 GACTTCTTCATCACCTTTTAG 3462GATTTTCCACTACTTCTTCAG NC_045512.2_21mer_win1_06409 6409 6429 2481ACTTCTTCATCACCTTTTAGG 3463 GGATTTTCCACTACTTCTTCANC_045512.2_21mer_win1_06410 6410 6430 2482 CTTCTTCATCACCTTTTAGGA 3464AGGATTTTCCACTACTTCTTC NC_045512.2_21mer_win1_06411 6411 6431 2483TTCTTCATCACCTTTTAGGAT 3465 TAGGATTTTCCACTACTTCTTNC_045512.2_21mer_win1_06412 6412 6432 2484 TCTTCATCACCTTTTAGGATG 3466GTAGGATTTTCCACTACTTCT NC_045512.2_21mer_win1_06413 6413 6433 2485CTTCATCACCTTTTAGGATGG 3467 GGTAGGATTTTCCACTACTTCNC_045512.2_21mer_win1_06461 6461 6481 2486 CACTTTTGATGGCTTCAACAT 3468TACAACTTCGGTAGTTTTCAC NC_045512.2_21mer_win1_06462 6462 6482 2487ACTTTTGATGGCTTCAACATC 3469 CTACAACTTCGGTAGTTTTCANC_045512.2_21mer_win1_06463 6463 6483 2488 CTTTTGATGGCTTCAACATCC 3470CCTACAACTTCGGTAGTTTTC NC_045512.2_21mer_win1_10484 10484 10504 2489AGTACACCATCACAACCAAAA 3471 AAAACCAACACTACCACATGANC_045512.2_21mer_win1_10485 10485 10505 2490 GTACACCATCACAACCAAAAT 3472TAAAACCAACACTACCACATG NC_045512.2_21mer_win1_10486 10486 10506 2491TACACCATCACAACCAAAATT 3473 TTAAAACCAACACTACCACATNC_045512.2_21mer_win1_10487 10487 10507 2492 ACACCATCACAACCAAAATTG 3474GTTAAAACCAACACTACCACA NC_045512.2_21mer_win1_10488 10488 10508 2493CACCATCACAACCAAAATTGT 3475 TGTTAAAACCAACACTACCACNC_045512.2_21mer_win1_10489 10489 10509 2494 ACCATCACAACCAAAATTGTA 3476ATGTTAAAACCAACACTACCA NC_045512.2_21mer_win1_11609 11609 11629 2495CAAATAACAAAGAATCCGATA 3477 ATAGCCTAAGAAACAATAAACNC_045512.2_21mer_win1_11610 11610 11630 2496 AAATAACAAAGAATCCGATAA 3478AATAGCCTAAGAAACAATAAA NC_045512.2_21mer_win1_12023 12023 12043 2497AGGTACGTCCCACGACATCTG 3479 GTCTACAGCACCCTGCATGGANC_045512.2_21mer_win1_12024 12024 12044 2498 GGTACGTCCCACGACATCTGT 3480TGTCTACAGCACCCTGCATGG NC_045512.2_21mer_win1_12025 12025 12045 2499GTACGTCCCACGACATCTGTA 3481 ATGTCTACAGCACCCTGCATGNC_045512.2_21mer_win1_12212 12212 12232 2500 AGAAACTTACACCGATTTAGA 3482AGATTTAGCCACATTCAAAGA NC_045512.2_21mer_win1_12213 12213 12233 2501GAAACTTACACCGATTTAGAC 3483 CAGATTTAGCCACATTCAAAGNC_045512.2_21mer_win1_12214 12214 12234 2502 AAACTTACACCGATTTAGACT 3484TCAGATTTAGCCACATTCAAA NC_045512.2_21mer_win1_12839 12839 12859 2503TTTACCCGATCTAAGGGATTC 3485 CTTAGGGAATCTAGCCCATTTNC_045512.2_21mer_win1_12840 12840 12860 2504 TTACCCGATCTAAGGGATTCT 3486TCTTAGGGAATCTAGCCCATT NC_045512.2_21mer_win1_12841 12841 12861 2505TACCCGATCTAAGGGATTCTC 3487 CTCTTAGGGAATCTAGCCCATNC_045512.2_21mer_win1_12842 12842 12862 2506 ACCCGATCTAAGGGATTCTCA 3488ACTCTTAGGGAATCTAGCCCA NC_045512.2_21mer_win1_12843 12843 12863 2507CCCGATCTAAGGGATTCTCAC 3489 CACTCTTAGGGAATCTAGCCCNC_045512.2_21mer_win1_12844 12844 12864 2508 CCGATCTAAGGGATTCTCACT 3490TCACTCTTAGGGAATCTAGCC NC_045512.2_21mer_win1_12845 12845 12865 2509CGATCTAAGGGATTCTCACTA 3491 ATCACTCTTAGGGAATCTAGCNC_045512.2_21mer_win1_12846 12846 12866 2510 GATCTAAGGGATTCTCACTAC 3492CATCACTCTTAGGGAATCTAG NC_045512.2_21mer_win1_12847 12847 12867 2511ATCTAAGGGATTCTCACTACC 3493 CCATCACTCTTAGGGAATCTANC_045512.2_21mer_win1_12885 12885 12905 2512 GTCTTGACCTTGGTGGAACAT 3494TACAAGGTGGTTCCAGTTCTG NC_045512.2_21mer_win1_12886 12886 12906 2513TCTTGACCTTGGTGGAACATC 3495 CTACAAGGTGGTTCCAGTTCTNC_045512.2_21mer_win1_12887 12887 12907 2514 CTTGACCTTGGTGGAACATCC 3496CCTACAAGGTGGTTCCAGTTC NC_045512.2_21mer_win1_12888 12888 12908 2515TTGACCTTGGTGGAACATCCA 3497 ACCTACAAGGTGGTTCCAGTTNC_045512.2_21mer_win1_12889 12889 12909 2516 TGACCTTGGTGGAACATCCAA 3498AACCTACAAGGTGGTTCCAGT NC_045512.2_21mer_win1_12890 12890 12910 2517GACCTTGGTGGAACATCCAAA 3499 AAACCTACAAGGTGGTTCCAGNC_045512.2_21mer_win1_12891 12891 12911 2518 ACCTTGGTGGAACATCCAAAC 3500CAAACCTACAAGGTGGTTCCA NC_045512.2_2lmer_win1_12892 12892 12912 2519CCTTGGTGGAACATCCAAACA 3501 ACAAACCTACAAGGTGGTTCCNC_045512.2_2lmer_win1_12893 12893 12913 2520 CTTGGTGGAACATCCAAACAA 3502AACAAACCTACAAGGTGGTTC NC_045512.2_2lmer_win1_12894 12894 12914 2521TTGGTGGAACATCCAAACAAT 3503 TAACAAACCTACAAGGTGGTTNC_045512.2_2lmer_win1_12895 12895 12915 2522 TGGTGGAACATCCAAACAATG 3504GTAACAAACCTACAAGGTGGT NC_045512.2_2lmer_win1_12896 12896 12916 2523GGTGGAACATCCAAACAATGT 3505 TGTAACAAACCTACAAGGTGGNC_045512.2_2lmer_win1_12897 12897 12917 2524 GTGGAACATCCAAACAATGTC 3506CTGTAACAAACCTACAAGGTG NC_045512.2_2lmer_win1_12898 12898 12918 2525TGGAACATCCAAACAATGTCT 3507 TCTGTAACAAACCTACAAGGTNC_045512.2_2lmer_win1_12899 12899 12919 2526 GGAACATCCAAACAATGTCTG 3508GTCTGTAACAAACCTACAAGG NC_045512.2_21mer_win1_12900 12900 12920 2527GAACATCCAAACAATGTCTGT 3509 TGTCTGTAACAAACCTACAAGNC_045512.2_2lmer_win1_12901 12901 12921 2528 AACATCCAAACAATGTCTGTG 3510GTGTCTGTAACAAACCTACAA NC_045512.2_2lmer_win1_12902 12902 12922 2529ACATCCAAACAATGTCTGTGT 3511 TGTGTCTGTAACAAACCTACANC_045512.2_2lmer_win1_12903 12903 12923 2530 CATCCAAACAATGTCTGTGTG 3512GTGTGTCTGTAACAAACCTAC NC_045512.2_2lmer_win1_12904 12904 12924 2531ATCCAAACAATGTCTGTGTGG 3513 GGTGTGTCTGTAACAAACCTANC_045512.2_2lmer_win1_12966 12966 12986 2532 ATTTGTTGGATTTATCTCCAT 3514TACCTCTATTTAGGTTGTTTA NC_045512.2_2lmer_win1_12967 12967 12987 2533TTTGTTGGATTTATCTCCATA 3515 ATACCTCTATTTAGGTTGTTTNC_045512.2_2lmer_win1_12968 12968 12988 2534 TTGTTGGATTTATCTCCATAC 3516CATACCTCTATTTAGGTTGTT NC_045512.2_2lmer_win1_12969 12969 12989 2535TGTTGGATTTATCTCCATACC 3517 CCATACCTCTATTTAGGTTGTNC_045512.2_2lmer_win1_12970 12970 12990 2536 GTTGGATTTATCTCCATACCA 3518ACCATACCTCTATTTAGGTTG NC_045512.2_2lmer_win1_13151 13151 13171 2537TTCTACAACACATGTGTGTGA 3519 AGTGTGTGTACACAACATCTTNC_045512.2_2lmer_win1_13152 13152 13172 2538 TCTACAACACATGTGTGTGAC 3520CAGTGTGTGTACACAACATCT NC_045512.2_2lmer_win1_13153 13153 13173 2539CTACAACACATGTGTGTGACC 3521 CCAGTGTGTGTACACAACATCNC_045512.2_2lmer_win1_13154 13154 13174 2540 TACAACACATGTGTGTGACCA 3522ACCAGTGTGTGTACACAACAT NC_045512.2_2lmer_win1_13155 13155 13175 2541ACAACACATGTGTGTGACCAT 3523 TACCAGTGTGTGTACACAACANC_045512.2_21mer_win1_13156 13156 13176 2542 CAACACATGTGTGTGACCATG 3524GTACCAGTGTGTGTACACAAC NC_045512.2_21mer_win1_13363 13363 13383 2543TTTGTGTCAGACATGGCAGAC 3525 CAGACGGTACAGACTGTGTTTNC_045512.2_21mer_win1_13364 13364 13384 2544 TTGTGTCAGACATGGCAGACG 3526GCAGACGGTACAGACTGTGTT NC_045512.2_21mer_win1_13365 13365 13385 2545TGTGTCAGACATGGCAGACGC 3527 CGCAGACGGTACAGACTGTGTNC_045512.2_21mer_win1_13366 13366 13386 2546 GTGTCAGACATGGCAGACGCC 3528CCGCAGACGGTACAGACTGTG NC_045512.2_21mer_win1_13388 13388 13408 2547TACACCTTTCCAATACCGACA 3529 ACAGCCATAACCTTTCCACATNC_045512.2_21mer_win1_13389 13389 13409 2548 ACACCTTTCCAATACCGACAT 3530TACAGCCATAACCTTTCCACA NC_045512.2_21mer_win1_13390 13390 13410 2549CACCTTTCCAATACCGACATC 3531 CTACAGCCATAACCTTTCCACNC_045512.2_21mer_win1_13391 13391 13411 2550 ACCTTTCCAATACCGACATCA 3532ACTACAGCCATAACCTTTCCA NC_045512.2_21mer_win1_13392 13392 13412 2551CCTTTCCAATACCGACATCAA 3533 AACTACAGCCATAACCTTTCCNC_045512.2_21mer_win1_13393 13393 13413 2552 CTTTCCAATACCGACATCAAC 3534CAACTACAGCCATAACCTTTC NC_045512.2_21mer_win1_13394 13394 13414 2553TTTCCAATACCGACATCAACA 3535 ACAACTACAGCCATAACCTTTNC_045512.2_21mer_win1_13395 13395 13415 2554 TTCCAATACCGACATCAACAC 3536CACAACTACAGCCATAACCTT NC_045512.2_21mer_win1_13396 13396 13416 2555TCCAATACCGACATCAACACT 3537 TCACAACTACAGCCATAACCTNC_045512.2_21mer_win1_13458 13458 13478 2556 GCAAAAATTTGCCCAAACGCC 3538CCGCAAACCCGTTTAAAAACG NC_045512.2_21mer_win1_13459 13459 13479 2557CAAAAATTTGCCCAAACGCCA 3539 ACCGCAAACCCGTTTAAAAACNC_045512.2_21mer_win1_13460 13460 13480 2558 AAAAATTTGCCCAAACGCCAC 3540CACCGCAAACCCGTTTAAAAA NC_045512.2_21mer_win1_13461 13461 13481 2559AAAATTTGCCCAAACGCCACA 3541 ACACCGCAAACCCGTTTAAAANC_045512.2_21mer_win1_13462 13462 13482 2560 AAATTTGCCCAAACGCCACAT 3542TACACCGCAAACCCGTTTAAA NC_045512.2_21mer_win1_13463 13463 13483 2561AATTTGCCCAAACGCCACATT 3543 TTACACCGCAAACCCGTTTAANC_045512.2_21mer_win1_13464 13464 13484 2562 ATTTGCCCAAACGCCACATTC 3544CTTACACCGCAAACCCGTTTA NC_045512.2_21mer_win1_13465 13465 13485 2563TTTGCCCAAACGCCACATTCA 3545 ACTTACACCGCAAACCCGTTTNC_045512.2_21mer_win1_13466 13466 13486 2564 TTGCCCAAACGCCACATTCAC 3546CACTTACACCGCAAACCCGTT NC_045512.2_21mer_win1_13467 13467 13487 2565TGCCCAAACGCCACATTCACG 3547 GCACTTACACCGCAAACCCGTNC_045512.2_21mer_win1_13468 13468 13488 2566 GCCCAAACGCCACATTCACGT 3548TGCACTTACACCGCAAACCCG NC_045512.2_21mer_win1_13469 13469 13489 2567CCCAAACGCCACATTCACGTC 3549 CTGCACTTACACCGCAAACCCNC_045512.2_21mer_win1_13470 13470 13490 2568 CCAAACGCCACATTCACGTCG 3550GCTGCACTTACACCGCAAACC NC_045512.2_21mer_win1_13471 13471 13491 2569CAAACGCCACATTCACGTCGG 3551 GGCTGCACTTACACCGCAAACNC_045512.2_21mer_win1_13472 13472 13492 2570 AAACGCCACATTCACGTCGGG 3552GGGCTGCACTTACACCGCAAA NC_045512.2_21mer_win1_13473 13473 13493 2571AACGCCACATTCACGTCGGGC 3553 CGGGCTGCACTTACACCGCAANC_045512.2_21mer_win1_13474 13474 13494 2572 ACGCCACATTCACGTCGGGCA 3554ACGGGCTGCACTTACACCGCA NC_045512.2_21mer_win1_13475 13475 13495 2573CGCCACATTCACGTCGGGCAG 3555 GACGGGCTGCACTTACACCGCNC_045512.2_21mer_win1_13476 13476 13496 2574 GCCACATTCACGTCGGGCAGA 3556AGACGGGCTGCACTTACACCG NC_045512.2_21mer_win1_13477 13477 13497 2575CCACATTCACGTCGGGCAGAA 3557 AAGACGGGCTGCACTTACACCNC_045512.2_21mer_win1_13478 13478 13498 2576 CACATTCACGTCGGGCAGAAT 3558TAAGACGGGCTGCACTTACAC NC_045512.2_21mer_win1_13479 13479 13499 2577ACATTCACGTCGGGCAGAATG 3559 GTAAGACGGGCTGCACTTACANC_045512.2_21mer_win1_13480 13480 13500 2578 CATTCACGTCGGGCAGAATGT 3560TGTAAGACGGGCTGCACTTAC NC_045512.2_21mer_win1_13481 13481 13501 2579ATTCACGTCGGGCAGAATGTG 3561 GTGTAAGACGGGCTGCACTTANC_045512.2_21mer_win1_13482 13482 13502 2580 TTCACGTCGGGCAGAATGTGG 3562GGTGTAAGACGGGCTGCACTT NC_045512.2_21mer_win1_13483 13483 13503 2581TCACGTCGGGCAGAATGTGGC 3563 CGGTGTAAGACGGGCTGCACTNC_045512.2_21mer_win1_13484 13484 13504 2582 CACGTCGGGCAGAATGTGGCA 3564ACGGTGTAAGACGGGCTGCAC NC_045512.2_21mer_win1_13485 13485 13505 2583ACGTCGGGCAGAATGTGGCAC 3565 CACGGTGTAAGACGGGCTGCANC_045512.2_21mer_win1_13486 13486 13506 2584 CGTCGGGCAGAATGTGGCACG 3566GCACGGTGTAAGACGGGCTGC NC_045512.2_21mer_win1_13487 13487 13507 2585GTCGGGCAGAATGTGGCACGC 3567 CGCACGGTGTAAGACGGGCTGNC_045512.2_21mer_win1_13488 13488 13508 2586 TCGGGCAGAATGTGGCACGCC 3568CCGCACGGTGTAAGACGGGCT NC_045512.2_21mer_win1_13489 13489 13509 2587CGGGCAGAATGTGGCACGCCG 3569 GCCGCACGGTGTAAGACGGGCNC_045512.2_21mer_win1_13490 13490 13510 2588 GGGCAGAATGTGGCACGCCGT 3570TGCCGCACGGTGTAAGACGGG NC_045512.2_21mer_win1_13491 13491 13511 2589GGCAGAATGTGGCACGCCGTG 3571 GTGCCGCACGGTGTAAGACGGNC_045512.2_21mer_win1_13492 13492 13512 2590 GCAGAATGTGGCACGCCGTGT 3572TGTGCCGCACGGTGTAAGACG NC_045512.2_21mer_win1_13493 13493 13513 2591CAGAATGTGGCACGCCGTGTC 3573 CTGTGCCGCACGGTGTAAGACNC_045512.2_21mer_win1_13494 13494 13514 2592 AGAATGTGGCACGCCGTGTCC 3574CCTGTGCCGCACGGTGTAAGA NC_045512.2_21mer_win1_13495 13495 13515 2593GAATGTGGCACGCCGTGTCCG 3575 GCCTGTGCCGCACGGTGTAAGNC_045512.2_21mer_win1_13496 13496 13516 2594 AATGTGGCACGCCGTGTCCGT 3576TGCCTGTGCCGCACGGTGTAA NC_045512.2_21mer_win1_13497 13497 13517 2595ATGTGGCACGCCGTGTCCGTG 3577 GTGCCTGTGCCGCACGGTGTANC_045512.2_21mer_win1_13498 13498 13518 2596 TGTGGCACGCCGTGTCCGTGA 3578AGTGCCTGTGCCGCACGGTGT NC_045512.2_21mer_win1_13499 13499 13519 2597GTGGCACGCCGTGTCCGTGAT 3579 TAGTGCCTGTGCCGCACGGTGNC_045512.2_21mer_win1_13500 13500 13520 2598 TGGCACGCCGTGTCCGTGATC 3580CTAGTGCCTGTGCCGCACGGT NC_045512.2_21mer_win1_13762 13762 13782 2599CCACTGTACCATGGTGTATAT 3581 TATATGTGGTACCATGTCACCNC_045512.2_21mer_win1_13763 13763 13783 2600 CACTGTACCATGGTGTATATA 3582ATATATGTGGTACCATGTCAC NC_045512.2_21mer_win1_13764 13764 13784 2601ACTGTACCATGGTGTATATAG 3583 GATATATGTGGTACCATGTCANC_045512.2_21mer_win1_13765 13765 13785 2602 CTGTACCATGGTGTATATAGT 3584TGATATATGTGGTACCATGTC NC_045512.2_21mer_win1_13766 13766 13786 2603TGTACCATGGTGTATATAGTG 3585 GTGATATATGTGGTACCATGTNC_045512.2_21mer_win1_13767 13767 13787 2604 GTACCATGGTGTATATAGTGC 3586CGTGATATATGTGGTACCATG NC_045512.2_21mer_win1_13768 13768 13788 2605TACCATGGTGTATATAGTGCA 3587 ACGTGATATATGTGGTACCATNC_045512.2_21mer_win1_13769 13769 13789 2606 ACCATGGTGTATATAGTGCAG 3588GACGTGATATATGTGGTACCA NC_045512.2_21mer_win1_13770 13770 13790 2607CCATGGTGTATATAGTGCAGT 3589 TGACGTGATATATGTGGTACCNC_045512.2_21mer_win1_14290 14290 14310 2608 CTGGCAATAAAATTTATAACC 3590CCAATATTTAAAATAACGGTC NC_045512.2_21mer_win1_14291 14291 14311 2609TGGCAATAAAATTTATAACCC 3591 CCCAATATTTAAAATAACGGTNC_045512.2_21mer_win1_14292 14292 14312 2610 GGCAATAAAATTTATAACCCT 3592TCCCAATATTTAAAATAACGG NC_045512.2_21mer_win1_14404 14404 14424 2611GGTGGATGTTCAAAACCTGGT 3593 TGGTCCAAAACTTGTAGGTGGNC_045512.2_2lmer_win1_14405 14405 14425 2612 GTGGATGTTCAAAACCTGGTG 3594GTGGTCCAAAACTTGTAGGTG NC_045512.2_21mer_win1_14406 14406 14426 2613TGGATGTTCAAAACCTGGTGA 3595 AGTGGTCCAAAACTTGTAGGTNC_045512.2_21mer_win1_14407 14407 14427 2614 GGATGTTCAAAACCTGGTGAT 3596TAGTGGTCCAAAACTTGTAGG NC_045512.2_2lmer_win1_14408 14408 14428 2615GATGTTCAAAACCTGGTGATC 3597 CTAGTGGTCCAAAACTTGTAGNC_045512.2_2lmer_win1_14409 14409 14429 2616 ATGTTCAAAACCTGGTGATCA 3598ACTAGTGGTCCAAAACTTGTA NC_045512.2_2lmer_win1_14500 14500 14520 2617CATGTATTAGTCCTACATTTG 3599 GTTTACATCCTGATTATGTACNC_045512.2_2lmer_win1_14501 14501 14521 2618 ATGTATTAGTCCTACATTTGA 3600AGTTTACATCCTGATTATGTA NC_045512.2_2lmer_win1_14502 14502 14522 2619TGTATTAGTCCTACATTTGAA 3601 AAGTTTACATCCTGATTATGTNC_045512.2_2lmer_win1_14503 14503 14523 2620 GTATTAGTCCTACATTTGAAT 3602TAAGTTTACATCCTGATTATG NC_045512.2_2lmer_win1_14504 14504 14524 2621TATTAGTCCTACATTTGAATG 3603 GTAAGTTTACATCCTGATTATNC_045512.2_2lmer_win1_14505 14505 14525 2622 ATTAGTCCTACATTTGAATGT 3604TGTAAGTTTACATCCTGATTA NC_045512.2_2lmer_win1_14506 14506 14526 2623TTAGTCCTACATTTGAATGTA 3605 ATGTAAGTTTACATCCTGATTNC_045512.2_2lmer_win1_14507 14507 14527 2624 TAGTCCTACATTTGAATGTAT 3606TATGTAAGTTTACATCCTGAT NC_045512.2_2lmer_win1_14508 14508 14528 2625AGTCCTACATTTGAATGTATC 3607 CTATGTAAGTTTACATCCTGANC_045512.2_2lmer_win1_14509 14509 14529 2626 GTCCTACATTTGAATGTATCG 3608GCTATGTAAGTTTACATCCTG NC_045512.2_2lmer_win1_14510 14510 14530 2627TCCTACATTTGAATGTATCGA 3609 AGCTATGTAAGTTTACATCCTNC_045512.2_2lmer_win1_14511 14511 14531 2628 CCTACATTTGAATGTATCGAG 3610GAGCTATGTAAGTTTACATCC NC_045512.2_2lmer_win1_14650 14650 14670 2629TTACAACGAAAAGTTTGACAG 3611 GACAGTTTGAAAAGCAACATTNC_045512.2_2lmer_win1_14651 14651 14671 2630 TACAACGAAAAGTTTGACAGT 3612TGACAGTTTGAAAAGCAACAT NC_045512.2_2lmer_win1_14652 14652 14672 2631ACAACGAAAAGTTTGACAGTT 3613 TTGACAGTTTGAAAAGCAACANC_045512.2_2lmer_win1_14653 14653 14673 2632 CAACGAAAAGTTTGACAGTTT 3614TTTGACAGTTTGAAAAGCAAC NC_045512.2_2lmer_win1_14654 14654 14674 2633AACGAAAAGTTTGACAGTTTG 3615 GTTTGACAGTTTGAAAAGCAANC_045512.2_21mer_win1_14655 14655 14675 2634 ACGAAAAGTTTGACAGTTTGG 3616GGTTTGACAGTTTGAAAAGCA NC_045512.2_21mer_win1_14656 14656 14676 2635CGAAAAGTTTGACAGTTTGGG 3617 GGGTTTGACAGTTTGAAAAGCNC_045512.2_21mer_win1_14657 14657 14677 2636 GAAAAGTTTGACAGTTTGGGC 3618CGGGTTTGACAGTTTGAAAAG NC_045512.2_21mer_win1_14658 14658 14678 2637AAAAGTTTGACAGTTTGGGCC 3619 CCGGGTTTGACAGTTTGAAAANC_045512.2_21mer_win1_14659 14659 14679 2638 AAAGTTTGACAGTTTGGGCCA 3620ACCGGGTTTGACAGTTTGAAA NC_045512.2_21mer_win1_14660 14660 14680 2639AAGTTTGACAGTTTGGGCCAT 3621 TACCGGGTTTGACAGTTTGAANC_045512.2_21mer_win1_14661 14661 14681 2640 AGTTTGACAGTTTGGGCCATT 3622TTACCGGGTTTGACAGTTTGA NC_045512.2_21mer_win1_14662 14662 14682 2641GTTTGACAGTTTGGGCCATTA 3623 ATTACCGGGTTTGACAGTTTGNC_045512.2_21mer_win1_14663 14663 14683 2642 TTTGACAGTTTGGGCCATTAA 3624AATTACCGGGTTTGACAGTTT NC_045512.2_21mer_win1_14664 14664 14684 2643TTGACAGTTTGGGCCATTAAA 3625 AAATTACCGGGTTTGACAGTTNC_045512.2_21mer_win1_14665 14665 14685 2644 TGACAGTTTGGGCCATTAAAA 3626AAAATTACCGGGTTTGACAGT NC_045512.2_21mer_win1_14666 14666 14686 2645GACAGTTTGGGCCATTAAAAT 3627 TAAAATTACCGGGTTTGACAGNC_045512.2_21mer_win1_14667 14667 14687 2646 ACAGTTTGGGCCATTAAAATT 3628TTAAAATTACCGGGTTTGACA NC_045512.2_21mer_win1_14722 14722 14742 2647AAGAAATTCCTTCCTTCAAGA 3629 AGAACTTCCTTCCTTAAAGAANC_045512.2_21mer_win1_14723 14723 14743 2648 AGAAATTCCTTCCTTCAAGAC 3630CAGAACTTCCTTCCTTAAAGA NC_045512.2_21mer_win1_14724 14724 14744 2649GAAATTCCTTCCTTCAAGACA 3631 ACAGAACTTCCTTCCTTAAAGNC_045512.2_21mer_win1_14725 14725 14745 2650 AAATTCCTTCCTTCAAGACAA 3632AACAGAACTTCCTTCCTTAAA NC_045512.2_21mer_win1_14726 14726 14746 2651AATTCCTTCCTTCAAGACAAC 3633 CAACAGAACTTCCTTCCTTAANC_045512.2_21mer_win1_14727 14727 14747 2652 ATTCCTTCCTTCAAGACAACT 3634TCAACAGAACTTCCTTCCTTA NC_045512.2_21mer_win1_14728 14728 14748 2653TTCCTTCCTTCAAGACAACTT 3635 TTCAACAGAACTTCCTTCCTTNC_045512.2_21mer_win1_14750 14750 14770 2654 ATTTTGTGAAGAAGAAACGAG 3636GAGCAAAGAAGAAGTGTTTTA NC_045512.2_21mer_win1_14751 14751 14771 2655TTTTGTGAAGAAGAAACGAGT 3637 TGAGCAAAGAAGAAGTGTTTTNC_045512.2_21mer_win1_14752 14752 14772 2656 TTTGTGAAGAAGAAACGAGTC 3638CTGAGCAAAGAAGAAGTGTTT NC_045512.2_21mer_win1_14753 14753 14773 2657TTGTGAAGAAGAAACGAGTCC 3639 CCTGAGCAAAGAAGAAGTGTTNC_045512.2_21mer_win1_14754 14754 14774 2658 TGTGAAGAAGAAACGAGTCCT 3640TCCTGAGCAAAGAAGAAGTGT NC_045512.2_21mer_win1_14755 14755 14775 2659GTGAAGAAGAAACGAGTCCTA 3641 ATCCTGAGCAAAGAAGAAGTGNC_045512.2_21mer_win1_14756 14756 14776 2660 TGAAGAAGAAACGAGTCCTAC 3642CATCCTGAGCAAAGAAGAAGT NC_045512.2_21mer_win1_14757 14757 14777 2661GAAGAAGAAACGAGTCCTACC 3643 CCATCCTGAGCAAAGAAGAAGNC_045512.2_21mer_win1_14821 14821 14841 2662 GGTTGTTACACACTATAGTCT 3644TCTGATATCACACATTGTTGG NC_045512.2_21mer_win1_14822 14822 14842 2663GTTGTTACACACTATAGTCTG 3645 GTCTGATATCACACATTGTTGNC_045512.2_21mer_win1_14823 14823 14843 2664 TTGTTACACACTATAGTCTGT 3646TGTCTGATATCACACATTGTT NC_045512.2_21mer_win1_14824 14824 14844 2665TGTTACACACTATAGTCTGTT 3647 TTGTCTGATATCACACATTGTNC_045512.2_21mer_win1_14825 14825 14845 2666 GTTACACACTATAGTCTGTTG 3648GTTGTCTGATATCACACATTG NC_045512.2_21mer_win1_14826 14826 14846 2667TTACACACTATAGTCTGTTGA 3649 AGTTGTCTGATATCACACATTNC_045512.2_21mer_win1_14875 14875 14895 2668 ATGAAACTAACAATGCTACCA 3650ACCATCGTAACAATCAAAGTA NC_045512.2_21mer_win1_14876 14876 14896 2669TGAAACTAACAATGCTACCAC 3651 CACCATCGTAACAATCAAAGTNC_045512.2_21mer_win1_14877 14877 14897 2670 GAAACTAACAATGCTACCACC 3652CCACCATCGTAACAATCAAAG NC_045512.2_21mer_win1_14878 14878 14898 2671AAACTAACAATGCTACCACCG 3653 GCCACCATCGTAACAATCAAANC_045512.2_21mer_win1_14879 14879 14899 2672 AACTAACAATGCTACCACCGA 3654AGCCACCATCGTAACAATCAA NC_045512.2_21mer_win1_14880 14880 14900 2673ACTAACAATGCTACCACCGAC 3655 CAGCCACCATCGTAACAATCANC_045512.2_21mer_win1_14881 14881 14901 2674 CTAACAATGCTACCACCGACA 3656ACAGCCACCATCGTAACAATC NC_045512.2_21mer_win1_14882 14882 14902 2675TAACAATGCTACCACCGACAT 3657 TACAGCCACCATCGTAACAATNC_045512.2_21mer_win1_14883 14883 14903 2676 AACAATGCTACCACCGACATA 3658ATACAGCCACCATCGTAACAA NC_045512.2_21mer_win1_14962 14962 14982 2677TTTACCCCATTCCGATCTGAA 3659 AAGTCTAGCCTTACCCCATTTNC_045512.2_21mer_win1_14963 14963 14983 2678 TTACCCCATTCCGATCTGAAA 3660AAAGTCTAGCCTTACCCCATT NC_045512.2_21mer_win1_14964 14964 14984 2679TACCCCATTCCGATCTGAAAT 3661 TAAAGTCTAGCCTTACCCCATNC_045512.2_21mer_win1_14965 14965 14985 2680 ACCCCATTCCGATCTGAAATA 3662ATAAAGTCTAGCCTTACCCCA NC_045512.2_21mer_win1_14966 14966 14986 2681CCCCATTCCGATCTGAAATAA 3663 AATAAAGTCTAGCCTTACCCCNC_045512.2_21mer_win1_14967 14967 14987 2682 CCCATTCCGATCTGAAATAAT 3664TAATAAAGTCTAGCCTTACCC NC_045512.2_21mer_win1_14968 14968 14988 2683CCATTCCGATCTGAAATAATA 3665 ATAATAAAGTCTAGCCTTACCNC_045512.2_21mer_win1_14969 14969 14989 2684 CATTCCGATCTGAAATAATAC 3666CATAATAAAGTCTAGCCTTAC NC_045512.2_21mer_win1_14970 14970 14990 2685ATTCCGATCTGAAATAATACT 3667 TCATAATAAAGTCTAGCCTTANC_045512.2_21mer_win1_14992 14992 15012 2686 AGTTACTCAATACTCCTAGTT 3668TTGATCCTCATAACTCATTGA NC_045512.2_21mer_win1_14993 14993 15013 2687GTTACTCAATACTCCTAGTTC 3669 CTTGATCCTCATAACTCATTGNC_045512.2_21mer_win1_14994 14994 15014 2688 TTACTCAATACTCCTAGTTCT 3670TCTTGATCCTCATAACTCATT NC_045512.2_21mer_win1_14995 14995 15015 2689TACTCAATACTCCTAGTTCTA 3671 ATCTTGATCCTCATAACTCATNC_045512.2_21mer_win1_14996 14996 15016 2690 ACTCAATACTCCTAGTTCTAC 3672CATCTTGATCCTCATAACTCA NC_045512.2_21mer_win1_14997 14997 15017 2691CTCAATACTCCTAGTTCTACG 3673 GCATCTTGATCCTCATAACTCNC_045512.2_21mer_win1_14998 14998 15018 2692 TCAATACTCCTAGTTCTACGT 3674TGCATCTTGATCCTCATAACT NC_045512.2_21mer_win1_14999 14999 15019 2693CAATACTCCTAGTTCTACGTG 3675 GTGCATCTTGATCCTCATAACNC_045512.2_21mer_win1_15000 15000 15020 2694 AATACTCCTAGTTCTACGTGA 3676AGTGCATCTTGATCCTCATAA NC_045512.2_21mer_win1_15055 15055 15075 2695TATTGAGTTTACTTAGAATTC 3677 CTTAAGATTCATTTGAGTTATNC_045512.2_21mer_win1_15056 15056 15076 2696 ATTGAGTTTACTTAGAATTCA 3678ACTTAAGATTCATTTGAGTTA NC_045512.2_21mer_win1_15057 15057 15077 2697TTGAGTTTACTTAGAATTCAT 3679 TACTTAAGATTCATTTGAGTTNC_045512.2_21mer_win1_15058 15058 15078 2698 TGAGTTTACTTAGAATTCATA 3680ATACTTAAGATTCATTTGAGT NC_045512.2_21mer_win1_15059 15059 15079 2699GAGTTTACTTAGAATTCATAC 3681 CATACTTAAGATTCATTTGAGNC_045512.2_21mer_win1_15060 15060 15080 2700 AGTTTACTTAGAATTCATACG 3682GCATACTTAAGATTCATTTGA NC_045512.2_21mer_win1_15061 15061 15081 2701GTTTACTTAGAATTCATACGG 3683 GGCATACTTAAGATTCATTTGNC_045512.2_21mer_win1_15062 15062 15082 2702 TTTACTTAGAATTCATACGGT 3684TGGCATACTTAAGATTCATTT NC_045512.2_2lmer_win1_15063 15063 15083 2703TTACTTAGAATTCATACGGTA 3685 ATGGCATACTTAAGATTCATTNC_045512.2_2lmer_win1_15064 15064 15084 2704 TACTTAGAATTCATACGGTAA 3686AATGGCATACTTAAGATTCAT NC_045512.2_2lmer_win1_15065 15065 15085 2705ACTTAGAATTCATACGGTAAT 3687 TAATGGCATACTTAAGATTCANC_045512.2_2lmer_win1_15066 15066 15086 2706 CTTAGAATTCATACGGTAATC 3688CTAATGGCATACTTAAGATTC NC_045512.2_2lmer_win1_15067 15067 15087 2707TTAGAATTCATACGGTAATCA 3689 ACTAATGGCATACTTAAGATTNC_045512.2_2lmer_win1_15068 15068 15088 2708 TAGAATTCATACGGTAATCAC 3690CACTAATGGCATACTTAAGAT NC_045512.2_2lmer_win1_15069 15069 15089 2709AGAATTCATACGGTAATCACG 3691 GCACTAATGGCATACTTAAGANC_045512.2_2lmer_win1_15070 15070 15090 2710 GAATTCATACGGTAATCACGT 3692TGCACTAATGGCATACTTAAG NC_045512.2_2lmer_win1_15071 15071 15091 2711AATTCATACGGTAATCACGTT 3693 TTGCACTAATGGCATACTTAANC_045512.2_2lmer_win1_15072 15072 15092 2712 ATTCATACGGTAATCACGTTT 3694TTTGCACTAATGGCATACTTA NC_045512.2_2lmer_win1_15073 15073 15093 2713TTCATACGGTAATCACGTTTC 3695 CTTTGCACTAATGGCATACTTNC_045512.2_2lmer_win1_15074 15074 15094 2714 TCATACGGTAATCACGTTTCT 3696TCTTTGCACTAATGGCATACT NC_045512.2_2lmer_win1_15075 15075 15095 2715CATACGGTAATCACGTTTCTT 3697 TTCTTTGCACTAATGGCATACNC_045512.2_2lmer_win1_15076 15076 15096 2716 ATACGGTAATCACGTTTCTTA 3698ATTCTTTGCACTAATGGCATA NC_045512.2_2lmer_win1_15077 15077 15097 2717TACGGTAATCACGTTTCTTAT 3699 TATTCTTTGCACTAATGGCATNC_045512.2_2lmer_win1_15078 15078 15098 2718 ACGGTAATCACGTTTCTTATC 3700CTATTCTTTGCACTAATGGCA NC_045512.2_2lmer_win1_15079 15079 15099 2719CGGTAATCACGTTTCTTATCT 3701 TCTATTCTTTGCACTAATGGCNC_045512.2_2lmer_win1_15080 15080 15100 2720 GGTAATCACGTTTCTTATCTC 3702CTCTATTCTTTGCACTAATGG NC_045512.2_2lmer_win1_15081 15081 15101 2721GTAATCACGTTTCTTATCTCG 3703 GCTCTATTCTTTGCACTAATGNC_045512.2_2lmer_win1_15082 15082 15102 2722 TAATCACGTTTCTTATCTCGA 3704AGCTCTATTCTTTGCACTAAT NC_045512.2_2lmer_win1_15083 15083 15103 2723AATCACGTTTCTTATCTCGAG 3705 GAGCTCTATTCTTTGCACTAANC_045512.2_2lmer_win1_15084 15084 15104 2724 ATCACGTTTCTTATCTCGAGC 3706CGAGCTCTATTCTTTGCACTA NC_045512.2_2lmer_win1_15085 15085 15105 2725TCACGTTTCTTATCTCGAGCG 3707 GCGAGCTCTATTCTTTGCACTNC_045512.2_21mer_win1_15086 15086 15106 2726 CACGTTTCTTATCTCGAGCGT 3708TGCGAGCTCTATTCTTTGCAC NC_045512.2_21mer_win1_15087 15087 15107 2727ACGTTTCTTATCTCGAGCGTG 3709 GTGCGAGCTCTATTCTTTGCANC_045512.2_21mer_win1_15088 15088 15108 2728 CGTTTCTTATCTCGAGCGTGG 3710GGTGCGAGCTCTATTCTTTGC NC_045512.2_21mer_win1_15089 15089 15109 2729GTTTCTTATCTCGAGCGTGGC 3711 CGGTGCGAGCTCTATTCTTTGNC_045512.2_21mer_win1_15090 15090 15110 2730 TTTCTTATCTCGAGCGTGGCA 3712ACGGTGCGAGCTCTATTCTTT NC_045512.2_21mer_win1_15091 15091 15111 2731TTCTTATCTCGAGCGTGGCAT 3713 TACGGTGCGAGCTCTATTCTTNC_045512.2_21mer_win1_15092 15092 15112 2732 TCTTATCTCGAGCGTGGCATC 3714CTACGGTGCGAGCTCTATTCT NC_045512.2_21mer_win1_15093 15093 15113 2733CTTATCTCGAGCGTGGCATCG 3715 GCTACGGTGCGAGCTCTATTCNC_045512.2_21mer_win1_15094 15094 15114 2734 TTATCTCGAGCGTGGCATCGA 3716AGCTACGGTGCGAGCTCTATT NC_045512.2_21mer_win1_15095 15095 15115 2735TATCTCGAGCGTGGCATCGAC 3717 CAGCTACGGTGCGAGCTCTATNC_045512.2_21mer_win1_15096 15096 15116 2736 ATCTCGAGCGTGGCATCGACC 3718CCAGCTACGGTGCGAGCTCTA NC_045512.2_21mer_win1_15097 15097 15117 2737TCTCGAGCGTGGCATCGACCA 3719 ACCAGCTACGGTGCGAGCTCTNC_045512.2_21mer_win1_15098 15098 15118 2738 CTCGAGCGTGGCATCGACCAC 3720CACCAGCTACGGTGCGAGCTC NC_045512.2_21mer_win1_15099 15099 15119 2739TCGAGCGTGGCATCGACCACA 3721 ACACCAGCTACGGTGCGAGCTNC_045512.2_21mer_win1_15100 15100 15120 2740 CGAGCGTGGCATCGACCACAG 3722GACACCAGCTACGGTGCGAGC NC_045512.2_21mer_win1_15101 15101 15121 2741GAGCGTGGCATCGACCACAGA 3723 AGACACCAGCTACGGTGCGAGNC_045512.2_21mer_win1_15102 15102 15122 2742 AGCGTGGCATCGACCACAGAG 3724GAGACACCAGCTACGGTGCGA NC_045512.2_21mer_win1_15103 15103 15123 2743GCGTGGCATCGACCACAGAGA 3725 AGAGACACCAGCTACGGTGCGNC_045512.2_21mer_win1_15104 15104 15124 2744 CGTGGCATCGACCACAGAGAT 3726TAGAGACACCAGCTACGGTGC NC_045512.2_21mer_win1_15105 15105 15125 2745GTGGCATCGACCACAGAGATA 3727 ATAGAGACACCAGCTACGGTGNC_045512.2_21mer_win1_15106 15106 15126 2746 TGGCATCGACCACAGAGATAG 3728GATAGAGACACCAGCTACGGT NC_045512.2_21mer_win1_15107 15107 15127 2747GGCATCGACCACAGAGATAGA 3729 AGATAGAGACACCAGCTACGGNC_045512.2_21mer_win1_15108 15108 15128 2748 GCATCGACCACAGAGATAGAC 3730CAGATAGAGACACCAGCTACG NC_045512.2_2lmer_win1_15109 15109 15129 2749CATCGACCACAGAGATAGACA 3731 ACAGATAGAGACACCAGCTACNC_045512.2_2lmer_win1_15110 15110 15130 2750 ATCGACCACAGAGATAGACAT 3732TACAGATAGAGACACCAGCTA NC_045512.2_2lmer_win1_15111 15111 15131 2751TCGACCACAGAGATAGACATC 3733 CTACAGATAGAGACACCAGCTNC_045512.2_2lmer_win1_15112 15112 15132 2752 CGACCACAGAGATAGACATCA 3734ACTACAGATAGAGACACCAGC NC_045512.2_2lmer_win1_15113 15113 15133 2753GACCACAGAGATAGACATCAT 3735 TACTACAGATAGAGACACCAGNC_045512.2_2lmer_win1_15114 15114 15134 2754 ACCACAGAGATAGACATCATG 3736GTACTACAGATAGAGACACCA NC_045512.2_2lmer_win1_15115 15115 15135 2755CCACAGAGATAGACATCATGA 3737 AGTACTACAGATAGAGACACCNC_045512.2_2lmer_win1_15116 15116 15136 2756 CACAGAGATAGACATCATGAT 3738TAGTACTACAGATAGAGACAC NC_045512.2_2lmer_win1_15117 15117 15137 2757ACAGAGATAGACATCATGATA 3739 ATAGTACTACAGATAGAGACANC_045512.2_2lmer_win1_15118 15118 15138 2758 CAGAGATAGACATCATGATAC 3740CATAGTACTACAGATAGAGAC NC_045512.2_2lmer_win1_15119 15119 15139 2759AGAGATAGACATCATGATACT 3741 TCATAGTACTACAGATAGAGANC_045512.2_2lmer_win1_15120 15120 15140 2760 GAGATAGACATCATGATACTG 3742GTCATAGTACTACAGATAGAG NC_045512.2_2lmer_win1_15172 15172 15192 2761AGTTATCGGCGGTGATCTCCT 3743 TCCTCTAGTGGCGGCTATTGANC_045512.2_2lmer_win1_15173 15173 15193 2762 GTTATCGGCGGTGATCTCCTC 3744CTCCTCTAGTGGCGGCTATTG NC_045512.2_2lmer_win1_15174 15174 15194 2763TTATCGGCGGTGATCTCCTCG 3745 GCTCCTCTAGTGGCGGCTATTNC_045512.2_2lmer_win1_15175 15175 15195 2764 TATCGGCGGTGATCTCCTCGA 3746AGCTCCTCTAGTGGCGGCTAT NC_045512.2_2lmer_win1_15176 15176 15196 2765ATCGGCGGTGATCTCCTCGAT 3747 TAGCTCCTCTAGTGGCGGCTANC_045512.2_2lmer_win1_15177 15177 15197 2766 TCGGCGGTGATCTCCTCGATG 3748GTAGCTCCTCTAGTGGCGGCT NC_045512.2_2lmer_win1_15178 15178 15198 2767CGGCGGTGATCTCCTCGATGA 3749 AGTAGCTCCTCTAGTGGCGGCNC_045512.2_2lmer_win1_15179 15179 15199 2768 GGCGGTGATCTCCTCGATGAC 3750CAGTAGCTCCTCTAGTGGCGG NC_045512.2_2lmer_win1_15180 15180 15200 2769GCGGTGATCTCCTCGATGACA 3751 ACAGTAGCTCCTCTAGTGGCGNC_045512.2_2lmer_win1_15310 15310 15330 2770 TCTCGGTACGGATTGTACGAA 3752AAGCATGTTAGGCATGGCTCT NC_045512.2_2lmer_win1_15311 15311 15331 2771CTCGGTACGGATTGTACGAAT 3753 TAAGCATGTTAGGCATGGCTCNC_045512.2_21mer_win1_15312 15312 15332 2772 TCGGTACGGATTGTACGAATC 3754CTAAGCATGTTAGGCATGGCT NC_045512.2_21mer_win1_15346 15346 15366 2773GAACAAGAACGAGCGTTTGTA 3755 ATGTTTGCGAGCAAGAACAAGNC_045512.2_21mer_win1_15347 15347 15367 2774 AACAAGAACGAGCGTTTGTAT 3756TATGTTTGCGAGCAAGAACAA NC_045512.2_21mer_win1_15496 15496 15516 2775TGTTGACGAATACGATTATCA 3757 ACTATTAGCATAAGCAGTTGTNC_045512.2_21mer_win1_15497 15497 15517 2776 GTTGACGAATACGATTATCAC 3758CACTATTAGCATAAGCAGTTG NC_045512.2_21mer_win1_15498 15498 15518 2777TTGACGAATACGATTATCACA 3759 ACACTATTAGCATAAGCAGTTNC_045512.2_21mer_win1_15622 15622 15642 2778 ATACTCACAGAGATATCTTTA 3760ATTTCTATAGAGACACTCATA NC_045512.2_21mer_win1_15623 15623 15643 2779TACTCACAGAGATATCTTTAT 3761 TATTTCTATAGAGACACTCATNC_045512.2_21mer_win1_15624 15624 15644 2780 ACTCACAGAGATATCTTTATC 3762CTATTTCTATAGAGACACTCA NC_045512.2_21mer_win1_15838 15838 15858 2781ACCTGACTCTGACTGGAATGA 3763 AGTAAGGTCAGTCTCAGTCCANC_045512.2_21mer_win1_15839 15839 15859 2782 CCTGACTCTGACTGGAATGAT 3764TAGTAAGGTCAGTCTCAGTCC NC_045512.2_21mer_win1_15840 15840 15860 2783CTGACTCTGACTGGAATGATT 3765 TTAGTAAGGTCAGTCTCAGTCNC_045512.2_21mer_win1_15841 15841 15861 2784 TGACTCTGACTGGAATGATTT 3766TTTAGTAAGGTCAGTCTCAGT NC_045512.2_21mer_win1_15842 15842 15862 2785GACTCTGACTGGAATGATTTC 3767 CTTTAGTAAGGTCAGTCTCAGNC_045512.2_21mer_win1_15843 15843 15863 2786 ACTCTGACTGGAATGATTTCC 3768CCTTTAGTAAGGTCAGTCTCA NC_045512.2_21mer_win1_15844 15844 15864 2787CTCTGACTGGAATGATTTCCT 3769 TCCTTTAGTAAGGTCAGTCTCNC_045512.2_21mer_win1_15845 15845 15865 2788 TCTGACTGGAATGATTTCCTG 3770GTCCTTTAGTAAGGTCAGTCT NC_045512.2_21mer_win1_15846 15846 15866 2789CTGACTGGAATGATTTCCTGG 3771 GGTCCTTTAGTAAGGTCAGTCNC_045512.2_21mer_win1_15847 15847 15867 2790 TGACTGGAATGATTTCCTGGA 3772AGGTCCTTTAGTAAGGTCAGT NC_045512.2_21mer_win1_15848 15848 15868 2791GACTGGAATGATTTCCTGGAG 3773 GAGGTCCTTTAGTAAGGTCAGNC_045512.2_21mer_win1_15849 15849 15869 2792 ACTGGAATGATTTCCTGGAGT 3774TGAGGTCCTTTAGTAAGGTCA NC_045512.2_21mer_win1_15985 15985 16005 2793TTTTGTCTACCATGTGAATAC 3775 CATAAGTGTACCATCTGTTTTNC_045512.2_21mer_win1_15986 15986 16006 2794 TTTGTCTACCATGTGAATACT 3776TCATAAGTGTACCATCTGTTT NC_045512.2_21mer_win1_15987 15987 16007 2795TTGTCTACCATGTGAATACTA 3777 ATCATAAGTGTACCATCTGTTNC_045512.2_21mer_win1_15988 15988 16008 2796 TGTCTACCATGTGAATACTAA 3778AATCATAAGTGTACCATCTGT NC_045512.2_21mer_win1_15989 15989 16009 2797GTCTACCATGTGAATACTAAC 3779 CAATCATAAGTGTACCATCTGNC_045512.2_21mer_win1_15990 15990 16010 2798 TCTACCATGTGAATACTAACT 3780TCAATCATAAGTGTACCATCT NC_045512.2_21mer_win1_16057 16057 16077 2799GGATTAGTCCTCATACGACTA 3781 ATCAGCATACTCCTGATTAGGNC_045512.2_21mer_win1_16058 16058 16078 2800 GATTAGTCCTCATACGACTAC 3782CATCAGCATACTCCTGATTAG NC_045512.2_21mer_win1_16059 16059 16079 2801ATTAGTCCTCATACGACTACA 3783 ACATCAGCATACTCCTGATTANC_045512.2_21mer_win1_16822 16822 16842 2802 CCTCTCATGTGGAAACTTTTT 3784TTTTTCAAAGGTGTACTCTCC NC_045512.2_21mer_win1_16823 16823 16843 2803CTCTCATGTGGAAACTTTTTC 3785 TTTTTCAAAGGTGTACTCTCNC_045512.2_21mer_win1_16824 16824 16844 2804 TCTCATGTGGAAACTTTTTCC 3786CCTTTTTCAAAGGTGTACTCT NC_045512.2_21mer_win1_16825 16825 16845 2805CTCATGTGGAAACTTTTTCCA 3787 ACCTTTTTCAAAGGTGTACTCNC_045512.2_21mer_win1_16826 16826 16846 2806 TCATGTGGAAACTTTTTCCAC 3788CACCTTTTTCAAAGGTGTACT NC_045512.2_21mer_win1_16827 16827 16847 2807CATGTGGAAACTTTTTCCACT 3789 TCACCTTTTTCAAAGGTGTACNC_045512.2_21mer_win1_16828 16828 16848 2808 ATGTGGAAACTTTTTCCACTG 3790GTCACCTTTTTCAAAGGTGTA NC_045512.2_21mer_win1_16829 16829 16849 2809TGTGGAAACTTTTTCCACTGA 3791 AGTCACCTTTTTCAAAGGTGTNC_045512.2_21mer_win1_16830 16830 16850 2810 GTGGAAACTTTTTCCACTGAT 3792TAGTCACCTTTTTCAAAGGTG NC_045512.2_21mer_win1_16831 16831 16851 2811TGGAAACTTTTTCCACTGATA 3793 ATAGTCACCTTTTTCAAAGGTNC_045512.2_21mer_win1_16832 16832 16852 2812 GGAAACTTTTTCCACTGATAC 3794CATAGTCACCTTTTTCAAAGG NC_045512.2_21mer_win1_16833 16833 16853 2813GAAACTTTTTCCACTGATACC 3795 CCATAGTCACCTTTTTCAAAGNC_045512.2_21mer_win1_16834 16834 16854 2814 AAACTTTTTCCACTGATACCA 3796ACCATAGTCACCTTTTTCAAA NC_045512.2_21mer_win1_16835 16835 16855 2815AACTTTTTCCACTGATACCAC 3797 CACCATAGTCACCTTTTTCAANC_045512.2_21mer_win1_16836 16836 16856 2816 ACTTTTTCCACTGATACCACT 3798TCACCATAGTCACCTTTTTCA NC_045512.2_21mer_win1_16837 16837 16857 2817CTTTTTCCACTGATACCACTA 3799 ATCACCATAGTCACCTTTTTCNC_045512.2_21mer_win1_16838 16838 16858 2818 TTTTTCCACTGATACCACTAC 3800CATCACCATAGTCACCTTTTT NC_045512.2_21mer_win1_16839 16839 16859 2819TTTTCCACTGATACCACTACG 3801 GCATCACCATAGTCACCTTTTNC_045512.2_21mer_win1_16840 16840 16860 2820 TTTCCACTGATACCACTACGA 3802AGCATCACCATAGTCACCTTT NC_045512.2_21mer_win1_16841 16841 16861 2821TTCCACTGATACCACTACGAC 3803 CAGCATCACCATAGTCACCTTNC_045512.2_21mer_win1_16842 16842 16862 2822 TCCACTGATACCACTACGACA 3804ACAGCATCACCATAGTCACCT NC_045512.2_21mer_win1_16843 16843 16863 2823CCACTGATACCACTACGACAA 3805 AACAGCATCACCATAGTCACCNC_045512.2_21mer_win1_16844 16844 16864 2824 CACTGATACCACTACGACAAC 3806CAACAGCATCACCATAGTCAC NC_045512.2_21mer_win1_16845 16845 16865 2825ACTGATACCACTACGACAACA 3807 ACAACAGCATCACCATAGTCANC_045512.2_21mer_win1_16954 16954 16974 2826 GATCACGGTGTTCTCGTGATA 3808ATAGTGCTCTTGTGGCACTAG NC_045512.2_21mer_win1_16955 16955 16975 2827ATCACGGTGTTCTCGTGATAC 3809 CATAGTGCTCTTGTGGCACTANC_045512.2_21mer_win1_16956 16956 16976 2828 TCACGGTGTTCTCGTGATACA 3810ACATAGTGCTCTTGTGGCACT NC_045512.2_21mer_win1_17008 17008 17028 2829TAGAGTCTACTCAAAAGATCG 3811 GCTAGAAAACTCATCTGAGATNC_045512.2_21mer_win1_17009 17009 17029 2830 AGAGTCTACTCAAAAGATCGT 3812TGCTAGAAAACTCATCTGAGA NC_045512.2_21mer_win1_17010 17010 17030 2831GAGTCTACTCAAAAGATCGTT 3813 TTGCTAGAAAACTCATCTGAGNC_045512.2_21mer_win1_17011 17011 17031 2832 AGTCTACTCAAAAGATCGTTA 3814ATTGCTAGAAAACTCATCTGA NC_045512.2_21mer_win1_17012 17012 17032 2833GTCTACTCAAAAGATCGTTAC 3815 CATTGCTAGAAAACTCATCTGNC_045512.2_21mer_win1_17013 17013 17033 2834 TCTACTCAAAAGATCGTTACA 3816ACATTGCTAGAAAACTCATCT NC_045512.2_21mer_win1_17014 17014 17034 2835CTACTCAAAAGATCGTTACAA 3817 AACATTGCTAGAAAACTCATCNC_045512.2_21mer_win1_17015 17015 17035 2836 TACTCAAAAGATCGTTACAAC 3818CAACATTGCTAGAAAACTCAT NC_045512.2_21mer_win1_17016 17016 17036 2837ACTCAAAAGATCGTTACAACG 3819 GCAACATTGCTAGAAAACTCANC_045512.2_21mer_win1_17017 17017 17037 2838 CTCAAAAGATCGTTACAACGT 3820TGCAACATTGCTAGAAAACTC NC_045512.2_21mer_win1_17018 17018 17038 2839TCAAAAGATCGTTACAACGTT 3821 TTGCAACATTGCTAGAAAACTNC_045512.2_21mer_win1_17019 17019 17039 2840 CAAAAGATCGTTACAACGTTT 3822TTTGCAACATTGCTAGAAAAC NC_045512.2_21mer_win1_17020 17020 17040 2841AAAAGATCGTTACAACGTTTA 3823 ATTTGCAACATTGCTAGAAAANC_045512.2_21mer_win1_17021 17021 17041 2842 AAAGATCGTTACAACGTTTAA 3824AATTTGCAACATTGCTAGAAA NC_045512.2_21mer_win1_17022 17022 17042 2843AAGATCGTTACAACGTTTAAT 3825 TAATTTGCAACATTGCTAGAANC_045512.2_21mer_win1_17080 17080 17100 2844 CCTGGTGGACCATGACCATTC 3826CTTACCAGTACCAGGTGGTCC NC_045512.2_21mer_win1_17081 17081 17101 2845CTGGTGGACCATGACCATTCT 3827 TCTTACCAGTACCAGGTGGTCNC_045512.2_21mer_win1_17082 17082 17102 2846 TGGTGGACCATGACCATTCTC 3828CTCTTACCAGTACCAGGTGGT NC_045512.2_21mer_win1_17083 17083 17103 2847GGTGGACCATGACCATTCTCA 3829 ACTCTTACCAGTACCAGGTGGNC_045512.2_21mer_win1_17084 17084 17104 2848 GTGGACCATGACCATTCTCAG 3830GACTCTTACCAGTACCAGGTG NC_045512.2_21mer_win1_17085 17085 17105 2849TGGACCATGACCATTCTCAGT 3831 TGACTCTTACCAGTACCAGGTNC_045512.2_21mer_win1_17086 17086 17106 2850 GGACCATGACCATTCTCAGTA 3832ATGACTCTTACCAGTACCAGG NC_045512.2_21mer_win1_17087 17087 17107 2851GACCATGACCATTCTCAGTAA 3833 AATGACTCTTACCAGTACCAGNC_045512.2_21mer_win1_17088 17088 17108 2852 ACCATGACCATTCTCAGTAAA 3834AAATGACTCTTACCAGTACCA NC_045512.2_21mer_win1_17089 17089 17109 2853CCATGACCATTCTCAGTAAAA 3835 AAAATGACTCTTACCAGTACCNC_045512.2_21mer_win1_17090 17090 17110 2854 CATGACCATTCTCAGTAAAAC 3836CAAAATGACTCTTACCAGTAC NC_045512.2_21mer_win1_17091 17091 17111 2855ATGACCATTCTCAGTAAAACG 3837 GCAAAATGACTCTTACCAGTANC_045512.2_21mer_win1_17269 17269 17289 2856 TTTAAGTTTCACTTAAGTTGT 3838TGTTGAATTCACTTTGAATTT NC_045512.2_21mer_win1_18100 18100 18120 2857TGTGTCCGTGGATGTGTGGAG 3839 GAGGTGTGTAGGTGCCTGTGTNC_045512.2_21mer_win1_18101 18101 18121 2858 GTGTCCGTGGATGTGTGGAGT 3840TGAGGTGTGTAGGTGCCTGTG NC_045512.2_21mer_win1_18102 18102 18122 2859TGTCCGTGGATGTGTGGAGTC 3841 CTGAGGTGTGTAGGTGCCTGTNC_045512.2_21mer_win1_18196 18196 18216 2860 TCTGAGTAGAGATACTACCCA 3842ACCCATCATAGAGATGAGTCT NC_045512.2_21mer_win1_18197 18197 18217 2861CTGAGTAGAGATACTACCCAA 3843 AACCCATCATAGAGATGAGTCNC_045512.2_21mer_win1_18198 18198 18218 2862 TGAGTAGAGATACTACCCAAA 3844AAACCCATCATAGAGATGAGT NC_045512.2_21mer_win1_19618 19618 19638 2863GTCTCAAATCTTTTACACCGA 3845 AGCCACATTTTCTAAACTCTGNC_045512.2_21mer_win1_19619 19619 19639 2864 TCTCAAATCTTTTACACCGAA 3846AAGCCACATTTTCTAAACTCT NC_045512.2_21mer_win1_20107 20107 20127 2865TTACCTCAGTGTAATTAACCT 3847 TCCAATTAATGTGACTCCATTNC_045512.2_21mer_win1_20108 20108 20128 2866 TACCTCAGTGTAATTAACCTC 3848CTCCAATTAATGTGACTCCAT NC_045512.2_21mer_win1_20109 20109 20129 2867ACCTCAGTGTAATTAACCTCT 3849 TCTCCAATTAATGTGACTCCANC_045512.2_21mer_win1_20110 20110 20130 2868 CCTCAGTGTAATTAACCTCTT 3850TTCTCCAATTAATGTGACTCC NC_045512.2_21mer_win1_21502 21502 21522 2869TAATCTCTTTTGTTGTCTCAA 3851 AACTCTGTTGTTTTCTCTAATNC_045512.2_21mer_win1_21503 21503 21523 2870 AATCTCTTTTGTTGTCTCAAC 3852CAACTCTGTTGTTTTCTCTAA NC_045512.2_21mer_win1_21504 21504 21524 2871ATCTCTTTTGTTGTCTCAACA 3853 ACAACTCTGTTGTTTTCTCTANC_045512.2_21mer_win1_24302 24302 24322 2872 TTACAAGAGATACTCTTGGTT 3854TTGGTTCTCATAGAGAACATT NC_045512.2_21mer_win1_24303 24303 24323 2873TACAAGAGATACTCTTGGTTT 3855 TTTGGTTCTCATAGAGAACATNC_045512.2_21mer_win1_24304 24304 24324 2874 ACAAGAGATACTCTTGGTTTT 3856TTTTGGTTCTCATAGAGAACA NC_045512.2_21mer_win1_24305 24305 24325 2875CAAGAGATACTCTTGGTTTTT 3857 TTTTTGGTTCTCATAGAGAACNC_045512.2_21mer_win1_24620 24620 24640 2876 CGAAGACGATTAGAACGACGA 3858AGCAGCAAGATTAGCAGAAGC NC_045512.2_21mer_win1_24621 24621 24641 2877GAAGACGATTAGAACGACGAT 3859 TAGCAGCAAGATTAGCAGAAGNC_045512.2_21mer_win1_24622 24622 24642 2878 AAGACGATTAGAACGACGATG 3860GTAGCAGCAAGATTAGCAGAA NC_045512.2_21mer_win1_24623 24623 24643 2879AGACGATTAGAACGACGATGA 3861 AGTAGCAGCAAGATTAGCAGANC_045512.2_21mer_win1_24624 24624 24644 2880 GACGATTAGAACGACGATGAT 3862TAGTAGCAGCAAGATTAGCAG NC_045512.2_21mer_win1_24625 24625 24645 2881ACGATTAGAACGACGATGATT 3863 TTAGTAGCAGCAAGATTAGCANC_045512.2_21mer_win1_24626 24626 24646 2882 CGATTAGAACGACGATGATTT 3864TTTAGTAGCAGCAAGATTAGC NC_045512.2_21mer_win1_24627 24627 24647 2883GATTAGAACGACGATGATTTT 3865 TTTTAGTAGCAGCAAGATTAGNC_045512.2_21mer_win1_24628 24628 24648 2884 ATTAGAACGACGATGATTTTA 3866ATTTTAGTAGCAGCAAGATTA NC_045512.2_21mer_win1_24629 24629 24649 2885TTAGAACGACGATGATTTTAC 3867 CATTTTAGTAGCAGCAAGATTNC_045512.2_21mer_win1_24630 24630 24650 2886 TAGAACGACGATGATTTTACA 3868ACATTTTAGTAGCAGCAAGAT NC_045512.2_21mer_win1_24631 24631 24651 2887AGAACGACGATGATTTTACAG 3869 GACATTTTAGTAGCAGCAAGANC_045512.2_21mer_win1_24662 24662 24682 2888 GAACCTGTTAGTTTTTCTCAA 3870AACTCTTTTTGATTGTCCAAG NC_045512.2_21mer_win1_24663 24663 24683 2889AACCTGTTAGTTTTTCTCAAC 3871 CAACTCTTTTTGATTGTCCAANC_045512.2_21mer_win1_24664 24664 24684 2890 ACCTGTTAGTTTTTCTCAACT 3872TCAACTCTTTTTGATTGTCCA NC_045512.2_21mer_win1_25034 25034 25054 2891TTAGTATGTAGTGGTCTACAA 3873 AACATCTGGTGATGTATGATTNC_045512.2_2lmer_win1_25035 25035 25055 2892 TAGTATGTAGTGGTCTACAAC 3874CAACATCTGGTGATGTATGAT NC_045512.2_21mer_win1_25036 25036 25056 2893AGTATGTAGTGGTCTACAACT 3875 TCAACATCTGGTGATGTATGANC_045512.2_21mer_win1_25037 25037 25057 2894 GTATGTAGTGGTCTACAACTA 3876ATCAACATCTGGTGATGTATG NC_045512.2_2lmer_win1_25104 25104 25124 2895TTCTTTAACTGGCGGAGTTAC 3877 CATTGAGGCGGTCAATTTCTTNC_045512.2_2lmer_win1_25105 25105 25125 2896 TCTTTAACTGGCGGAGTTACT 3878TCATTGAGGCGGTCAATTTCT NC_045512.2_2lmer_win1_25106 25106 25126 2897CTTTAACTGGCGGAGTTACTC 3879 CTCATTGAGGCGGTCAATTTCNC_045512.2_2lmer_win1_25107 25107 25127 2898 TTTAACTGGCGGAGTTACTCC 3880CCTCATTGAGGCGGTCAATTT NC_045512.2_2lmer_win1_25108 25108 25128 2899TTAACTGGCGGAGTTACTCCA 3881 ACCTCATTGAGGCGGTCAATTNC_045512.2_21mer_win1_25364 25364 25384 2900 CAGTTTAATGTAATGTGTATT 3882TTATGTGTAATGTAATTTGAC NC_045512.2_21mer_win1_25365 25365 25385 2901AGTTTAATGTAATGTGTATTT 3883 TTTATGTGTAATGTAATTTGANC_045512.2_21mer_win1_25366 25366 25386 2902 GTTTAATGTAATGTGTATTTG 3884GTTTATGTGTAATGTAATTTG NC_045512.2_21mer_win1_25367 25367 25387 2903TTTAATGTAATGTGTATTTGC 3885 CGTTTATGTGTAATGTAATTTNC_045512.2_21mer_win1_25502 25502 25522 2904 ATGTTCGGAGTGAGGGAAAGC 3886CGAAAGGGAGTGAGGCTTGTA NC_045512.2_21mer_win1_25503 25503 25523 2905TGTTCGGAGTGAGGGAAAGCC 3887 CCGAAAGGGAGTGAGGCTTGTNC_045512.2_21mer_win1_25504 25504 25524 2906 GTTCGGAGTGAGGGAAAGCCT 3888TCCGAAAGGGAGTGAGGCTTG NC_045512.2_21mer_win1_25505 25505 25525 2907TTCGGAGTGAGGGAAAGCCTA 3889 ATCCGAAAGGGAGTGAGGCTTNC_045512.2_21mer_win1_25506 25506 25526 2908 TCGGAGTGAGGGAAAGCCTAC 3890CATCCGAAAGGGAGTGAGGCT NC_045512.2_21mer_win1_25507 25507 25527 2909CGGAGTGAGGGAAAGCCTACC 3891 CCATCCGAAAGGGAGTGAGGCNC_045512.2_21mer_win1_25508 25508 25528 2910 GGAGTGAGGGAAAGCCTACCG 3892GCCATCCGAAAGGGAGTGAGG NC_045512.2_21mer_win1_25509 25509 25529 2911GAGTGAGGGAAAGCCTACCGA 3893 AGCCATCCGAAAGGGAGTGAGNC_045512.2_21mer_win1_25510 25510 25530 2912 AGTGAGGGAAAGCCTACCGAA 3894AAGCCATCCGAAAGGGAGTGA NC_045512.2_21mer_win1_26191 26191 26211 2913GGCTGCTGCTGATGATCGCAC 3895 CACGCTAGTAGTCGTCGTCGGNC_045512.2_21mer_win1_26192 26192 26212 2914 GCTGCTGCTGATGATCGCACG 3896GCACGCTAGTAGTCGTCGTCG NC_045512.2_21mer_win1_26193 26193 26213 2915CTGCTGCTGATGATCGCACGG 3897 GGCACGCTAGTAGTCGTCGTCNC_045512.2_21mer_win1_26194 26194 26214 2916 TGCTGCTGATGATCGCACGGA 3898AGGCACGCTAGTAGTCGTCGT NC_045512.2_21mer_win1_26195 26195 26215 2917GCTGCTGATGATCGCACGGAA 3899 AAGGCACGCTAGTAGTCGTCGNC_045512.2_21mer_win1_26196 26196 26216 2918 CTGCTGATGATCGCACGGAAA 3900AAAGGCACGCTAGTAGTCGTC NC_045512.2_21mer_win1_26197 26197 26217 2919TGCTGATGATCGCACGGAAAC 3901 CAAAGGCACGCTAGTAGTCGTNC_045512.2_21mer_win1_26198 26198 26218 2920 GCTGATGATCGCACGGAAACA 3902ACAAAGGCACGCTAGTAGTCG NC_045512.2_21mer_win1_26199 26199 26219 2921CTGATGATCGCACGGAAACAT 3903 TACAAAGGCACGCTAGTAGTCNC_045512.2_21mer_win1_26200 26200 26220 2922 TGATGATCGCACGGAAACATT 3904TTACAAAGGCACGCTAGTAGT NC_045512.2_21mer_win1_26201 26201 26221 2923GATGATCGCACGGAAACATTC 3905 CTTACAAAGGCACGCTAGTAGNC_045512.2_21mer_win1_26202 26202 26222 2924 ATGATCGCACGGAAACATTCG 3906GCTTACAAAGGCACGCTAGTA NC_045512.2_21mer_win1_26203 26203 26223 2925TGATCGCACGGAAACATTCGT 3907 TGCTTACAAAGGCACGCTAGTNC_045512.2_21mer_win1_26204 26204 26224 2926 GATCGCACGGAAACATTCGTG 3908GTGCTTACAAAGGCACGCTAG NC_045512.2_21mer_win1_26205 26205 26225 2927ATCGCACGGAAACATTCGTGT 3909 TGTGCTTACAAAGGCACGCTANC_045512.2_21mer_win1_26206 26206 26226 2928 TCGCACGGAAACATTCGTGTT 3910TTGTGCTTACAAAGGCACGCT NC_045512.2_21mer_win1_26207 26207 26227 2929CGCACGGAAACATTCGTGTTC 3911 CTTGTGCTTACAAAGGCACGCNC_045512.2_21mer_win1_26232 26232 26252 2930 ACTCATGCTTGAATACATGAG 3912GAGTACATAAGTTCGTACTCA NC_045512.2_21mer_win1_26233 26233 26253 2931CTCATGCTTGAATACATGAGT 3913 TGAGTACATAAGTTCGTACTCNC_045512.2_21mer_win1_26234 26234 26254 2932 TCATGCTTGAATACATGAGTA 3914ATGAGTACATAAGTTCGTACT NC_045512.2_21mer_win1_26235 26235 26255 2933CATGCTTGAATACATGAGTAA 3915 AATGAGTACATAAGTTCGTACNC_045512.2_21mer_win1_26236 26236 26256 2934 ATGCTTGAATACATGAGTAAG 3916GAATGAGTACATAAGTTCGTA NC_045512.2_21mer_win1_26237 26237 26257 2935TGCTTGAATACATGAGTAAGC 3917 CGAATGAGTACATAAGTTCGTNC_045512.2_21mer_win1_26238 26238 26258 2936 GCTTGAATACATGAGTAAGCA 3918ACGAATGAGTACATAAGTTCG NC_045512.2_21mer_win1_26239 26239 26259 2937CTTGAATACATGAGTAAGCAA 3919 AACGAATGAGTACATAAGTTCNC_045512.2_21mer_win1_26240 26240 26260 2938 TTGAATACATGAGTAAGCAAA 3920AAACGAATGAGTACATAAGTT NC_045512.2_21mer_win1_26241 26241 26261 2939TGAATACATGAGTAAGCAAAG 3921 GAAACGAATGAGTACATAAGTNC_045512.2_21mer_win1_26242 26242 26262 2940 GAATACATGAGTAAGCAAAGC 3922CGAAACGAATGAGTACATAAG NC_045512.2_21mer_win1_26243 26243 26263 2941AATACATGAGTAAGCAAAGCC 3923 CCGAAACGAATGAGTACATAANC_045512.2_21mer_win1_26244 26244 26264 2942 ATACATGAGTAAGCAAAGCCT 3924TCCGAAACGAATGAGTACATA NC_045512.2_21mer_win1_26245 26245 26265 2943TACATGAGTAAGCAAAGCCTT 3925 TTCCGAAACGAATGAGTACATNC_045512.2_21mer_win1_26246 26246 26266 2944 ACATGAGTAAGCAAAGCCTTC 3926CTTCCGAAACGAATGAGTACA NC_045512.2_21mer_win1_26247 26247 26267 2945CATGAGTAAGCAAAGCCTTCT 3927 TCTTCCGAAACGAATGAGTACNC_045512.2_21mer_win1_26269 26269 26289 2946 TGTCCATGCAATTATCAATTA 3928ATTAACTATTAACGTACCTGT NC_045512.2_21mer_win1_26270 26270 26290 2947GTCCATGCAATTATCAATTAT 3929 TATTAACTATTAACGTACCTGNC_045512.2_21mer_win1_26271 26271 26291 2948 TCCATGCAATTATCAATTATC 3930CTATTAACTATTAACGTACCT NC_045512.2_21mer_win1_26272 26272 26292 2949CCATGCAATTATCAATTATCG 3931 GCTATTAACTATTAACGTACCNC_045512.2_21mer_win1_26273 26273 26293 2950 CATGCAATTATCAATTATCGC 3932CGCTATTAACTATTAACGTAC NC_045512.2_21mer_win1_26274 26274 26294 2951ATGCAATTATCAATTATCGCA 3933 ACGCTATTAACTATTAACGTANC_045512.2_21mer_win1_26275 26275 26295 2952 TGCAATTATCAATTATCGCAT 3934TACGCTATTAACTATTAACGT NC_045512.2_21mer_win1_26276 26276 26296 2953GCAATTATCAATTATCGCATG 3935 GTACGCTATTAACTATTAACGNC_045512.2_21mer_win1_26277 26277 26297 2954 CAATTATCAATTATCGCATGA 3936AGTACGCTATTAACTATTAAC NC_045512.2_21mer_win1_26278 26278 26298 2955AATTATCAATTATCGCATGAA 3937 AAGTACGCTATTAACTATTAANC_045512.2_21mer_win1_26279 26279 26299 2956 ATTATCAATTATCGCATGAAG 3938GAAGTACGCTATTAACTATTA NC_045512.2_21mer_win1_26280 26280 26300 2957TTATCAATTATCGCATGAAGA 3939 AGAAGTACGCTATTAACTATTNC_045512.2_21mer_win1_26281 26281 26301 2958 TATCAATTATCGCATGAAGAA 3940AAGAAGTACGCTATTAACTAT NC_045512.2_21mer_win1_26282 26282 26302 2959ATCAATTATCGCATGAAGAAA 3941 AAAGAAGTACGCTATTAACTANC_045512.2_21mer_win1_26283 26283 26303 2960 TCAATTATCGCATGAAGAAAA 3942AAAAGAAGTACGCTATTAACT NC_045512.2_21mer_win1_26284 26284 26304 2961CAATTATCGCATGAAGAAAAA 3943 AAAAAGAAGTACGCTATTAACNC_045512.2_21mer_win1_26285 26285 26305 2962 AATTATCGCATGAAGAAAAAG 3944GAAAAAGAAGTACGCTATTAA NC_045512.2_21mer_win1_26286 26286 26306 2963ATTATCGCATGAAGAAAAAGA 3945 AGAAAAAGAAGTACGCTATTANC_045512.2_21mer_win1_26287 26287 26307 2964 TTATCGCATGAAGAAAAAGAA 3946AAGAAAAAGAAGTACGCTATT NC_045512.2_21mer_win1_26288 26288 26308 2965TATCGCATGAAGAAAAAGAAC 3947 CAAGAAAAAGAAGTACGCTATNC_045512.2_21mer_win1_26289 26289 26309 2966 ATCGCATGAAGAAAAAGAACG 3948GCAAGAAAAAGAAGTACGCTA NC_045512.2_21mer_win1_26290 26290 26310 2967TCGCATGAAGAAAAAGAACGA 3949 AGCAAGAAAAAGAAGTACGCTNC_045512.2_21mer_win1_26291 26291 26311 2968 CGCATGAAGAAAAAGAACGAA 3950AAGCAAGAAAAAGAAGTACGC NC_045512.2_21mer_win1_26292 26292 26312 2969GCATGAAGAAAAAGAACGAAA 3951 AAAGCAAGAAAAAGAAGTACGNC_045512.2_21mer_win1_26293 26293 26313 2970 CATGAAGAAAAAGAACGAAAG 3952GAAAGCAAGAAAAAGAAGTAC NC_045512.2_21mer_win1_26294 26294 26314 2971ATGAAGAAAAAGAACGAAAGC 3953 CGAAAGCAAGAAAAAGAAGTANC_045512.2_21mer_win1_26295 26295 26315 2972 TGAAGAAAAAGAACGAAAGCA 3954ACGAAAGCAAGAAAAAGAAGT NC_045512.2_21mer_win1_26296 26296 26316 2973GAAGAAAAAGAACGAAAGCAC 3955 CACGAAAGCAAGAAAAAGAAGNC_045512.2_21mer_win1_26297 26297 26317 2974 AAGAAAAAGAACGAAAGCACC 3956CCACGAAAGCAAGAAAAAGAA NC_045512.2_21mer_win1_26298 26298 26318 2975AGAAAAAGAACGAAAGCACCA 3957 ACCACGAAAGCAAGAAAAAGANC_045512.2_21mer_win1_26299 26299 26319 2976 GAAAAAGAACGAAAGCACCAT 3958TACCACGAAAGCAAGAAAAAG NC_045512.2_21mer_win1_26300 26300 26320 2977AAAAAGAACGAAAGCACCATA 3959 ATACCACGAAAGCAAGAAAAANC_045512.2_21mer_win1_26301 26301 26321 2978 AAAAGAACGAAAGCACCATAA 3960AATACCACGAAAGCAAGAAAA NC_045512.2_21mer_win1_26302 26302 26322 2979AAAGAACGAAAGCACCATAAG 3961 GAATACCACGAAAGCAAGAAANC_045512.2_21mer_win1_26303 26303 26323 2980 AAGAACGAAAGCACCATAAGA 3962AGAATACCACGAAAGCAAGAA NC_045512.2_21mer_win1_26304 26304 26324 2981AGAACGAAAGCACCATAAGAA 3963 AAGAATACCACGAAAGCAAGANC_045512.2_21mer_win1_26305 26305 26325 2982 GAACGAAAGCACCATAAGAAC 3964CAAGAATACCACGAAAGCAAG NC_045512.2_21mer_win1_26306 26306 26326 2983AACGAAAGCACCATAAGAACG 3965 GCAAGAATACCACGAAAGCAANC_045512.2_21mer_win1_26307 26307 26327 2984 ACGAAAGCACCATAAGAACGA 3966AGCAAGAATACCACGAAAGCA NC_045512.2_21mer_win1_26308 26308 26328 2985CGAAAGCACCATAAGAACGAT 3967 TAGCAAGAATACCACGAAAGCNC_045512.2_21mer_win1_26309 26309 26329 2986 GAAAGCACCATAAGAACGATC 3968CTAGCAAGAATACCACGAAAG NC_045512.2_21mer_win1_26310 26310 26330 2987AAAGCACCATAAGAACGATCA 3969 ACTAGCAAGAATACCACGAAANC_045512.2_21mer_win1_26332 26332 26352 2988 TGTGATCGGTAGGAATGACGC 3970CGCAGTAAGGATGGCTAGTGT NC_045512.2_21mer_win1_26333 26333 26353 2989GTGATCGGTAGGAATGACGCG 3971 GCGCAGTAAGGATGGCTAGTGNC_045512.2_21mer_win1_26334 26334 26354 2990 TGATCGGTAGGAATGACGCGA 3972AGCGCAGTAAGGATGGCTAGT NC_045512.2_21mer_win1_26335 26335 26355 2991GATCGGTAGGAATGACGCGAA 3973 AAGCGCAGTAAGGATGGCTAGNC_045512.2_21mer_win1_26336 26336 26356 2992 ATCGGTAGGAATGACGCGAAG 3974GAAGCGCAGTAAGGATGGCTA NC_045512.2_21mer_win1_26337 26337 26357 2993TCGGTAGGAATGACGCGAAGC 3975 CGAAGCGCAGTAAGGATGGCTNC_045512.2_21mer_win1_26338 26338 26358 2994 CGGTAGGAATGACGCGAAGCT 3976TCGAAGCGCAGTAAGGATGGC NC_045512.2_21mer_win1_26339 26339 26359 2995GGTAGGAATGACGCGAAGCTA 3977 ATCGAAGCGCAGTAAGGATGGNC_045512.2_21mer_win1_26340 26340 26360 2996 GTAGGAATGACGCGAAGCTAA 3978AATCGAAGCGCAGTAAGGATG NC_045512.2_21mer_win1_26341 26341 26361 2997TAGGAATGACGCGAAGCTAAC 3979 CAATCGAAGCGCAGTAAGGATNC_045512.2_21mer_win1_26342 26342 26362 2998 AGGAATGACGCGAAGCTAACA 3980ACAATCGAAGCGCAGTAAGGA NC_045512.2_21mer_win1_26343 26343 26363 2999GGAATGACGCGAAGCTAACAC 3981 CACAATCGAAGCGCAGTAAGGNC_045512.2_21mer_win1_26344 26344 26364 3000 GAATGACGCGAAGCTAACACA 3982ACACAATCGAAGCGCAGTAAG NC_045512.2_21mer_win1_26345 26345 26365 3001AATGACGCGAAGCTAACACAC 3983 CACACAATCGAAGCGCAGTAANC_045512.2_21mer_win1_26346 26346 26366 3002 ATGACGCGAAGCTAACACACG 3984GCACACAATCGAAGCGCAGTA NC_045512.2_21mer_win1_26347 26347 26367 3003TGACGCGAAGCTAACACACGC 3985 CGCACACAATCGAAGCGCAGTNC_045512.2_21mer_win1_26348 26348 26368 3004 GACGCGAAGCTAACACACGCA 3986ACGCACACAATCGAAGCGCAG NC_045512.2_21mer_win1_26349 26349 26369 3005ACGCGAAGCTAACACACGCAT 3987 TACGCACACAATCGAAGCGCANC_045512.2_21mer_win1_26350 26350 26370 3006 CGCGAAGCTAACACACGCATG 3988GTACGCACACAATCGAAGCGC NC_045512.2_21mer_win1_26351 26351 26371 3007GCGAAGCTAACACACGCATGA 3989 AGTACGCACACAATCGAAGCGNC_045512.2_21mer_win1_26352 26352 26372 3008 CGAAGCTAACACACGCATGAC 3990CAGTACGCACACAATCGAAGC NC_045512.2_21mer_win1_26353 26353 26373 3009GAAGCTAACACACGCATGACG 3991 GCAGTACGCACACAATCGAAGNC_045512.2_21mer_win1_26354 26354 26374 3010 AAGCTAACACACGCATGACGA 3992AGCAGTACGCACACAATCGAA NC_045512.2_21mer_win1_26355 26355 26375 3011AGCTAACACACGCATGACGAC 3993 CAGCAGTACGCACACAATCGANC_045512.2_21mer_win1_26356 26356 26376 3012 GCTAACACACGCATGACGACG 3994GCAGCAGTACGCACACAATCG NC_045512.2_21mer_win1_26357 26357 26377 3013CTAACACACGCATGACGACGT 3995 TGCAGCAGTACGCACACAATCNC_045512.2_21mer_win1_26358 26358 26378 3014 TAACACACGCATGACGACGTT 3996TTGCAGCAGTACGCACACAAT NC_045512.2_21mer_win1_26359 26359 26379 3015AACACACGCATGACGACGTTA 3997 ATTGCAGCAGTACGCACACAANC_045512.2_21mer_win1_26360 26360 26380 3016 ACACACGCATGACGACGTTAT 3998TATTGCAGCAGTACGCACACA NC_045512.2_21mer_win1_26361 26361 26381 3017CACACGCATGACGACGTTATA 3999 ATATTGCAGCAGTACGCACACNC_045512.2_21mer_win1_26362 26362 26382 3018 ACACGCATGACGACGTTATAA 4000AATATTGCAGCAGTACGCACA NC_045512.2_21mer_win1_26363 26363 26383 3019CACGCATGACGACGTTATAAC 4001 CAATATTGCAGCAGTACGCACNC_045512.2_21mer_win1_26364 26364 26384 3020 ACGCATGACGACGTTATAACA 4002ACAATATTGCAGCAGTACGCA NC_045512.2_21mer_win1_26365 26365 26385 3021CGCATGACGACGTTATAACAA 4003 AACAATATTGCAGCAGTACGCNC_045512.2_21mer_win1_26366 26366 26386 3022 GCATGACGACGTTATAACAAT 4004TAACAATATTGCAGCAGTACG NC_045512.2_21mer_win1_26367 26367 26387 3023CATGACGACGTTATAACAATT 4005 TTAACAATATTGCAGCAGTACNC_045512.2_21mer_win1_26368 26368 26388 3024 ATGACGACGTTATAACAATTG 4006GTTAACAATATTGCAGCAGTA NC_045512.2_21mer_win1_26369 26369 26389 3025TGACGACGTTATAACAATTGC 4007 CGTTAACAATATTGCAGCAGTNC_045512.2_21mer_win1_26370 26370 26390 3026 GACGACGTTATAACAATTGCA 4008ACGTTAACAATATTGCAGCAG NC_045512.2_21mer_win1_26371 26371 26391 3027ACGACGTTATAACAATTGCAC 4009 CACGTTAACAATATTGCAGCANC_045512.2_21mer_win1_26372 26372 26392 3028 CGACGTTATAACAATTGCACT 4010TCACGTTAACAATATTGCAGC NC_045512.2_21mer_win1_26373 26373 26393 3029GACGTTATAACAATTGCACTC 4011 CTCACGTTAACAATATTGCAGNC_045512.2_21mer_win1_26374 26374 26394 3030 ACGTTATAACAATTGCACTCA 4012ACTCACGTTAACAATATTGCA NC_045512.2_21mer_win1_26450 26450 26470 3031CTCAAGGACTAGAAGACCAGA 4013 AGACCAGAAGATCAGGAACTCNC_045512.2_21mer_win1_26451 26451 26471 3032 TCAAGGACTAGAAGACCAGAT 4014TAGACCAGAAGATCAGGAACT NC_045512.2_21mer_win1_26452 26452 26472 3033CAAGGACTAGAAGACCAGATT 4015 TTAGACCAGAAGATCAGGAACNC_045512.2_21mer_win1_26453 26453 26473 3034 AAGGACTAGAAGACCAGATTT 4016TTTAGACCAGAAGATCAGGAA NC_045512.2_21mer_win1_26454 26454 26474 3035AGGACTAGAAGACCAGATTTG 4017 GTTTAGACCAGAAGATCAGGANC_045512.2_21mer_win1_26455 26455 26475 3036 GGACTAGAAGACCAGATTTGC 4018CGTTTAGACCAGAAGATCAGG NC_045512.2_21mer_win1_26456 26456 26476 3037GACTAGAAGACCAGATTTGCT 4019 TCGTTTAGACCAGAAGATCAGNC_045512.2_21mer_win1_26457 26457 26477 3038 ACTAGAAGACCAGATTTGCTT 4020TTCGTTTAGACCAGAAGATCA NC_045512.2_21mer_win1_26458 26458 26478 3039CTAGAAGACCAGATTTGCTTG 4021 GTTCGTTTAGACCAGAAGATCNC_045512.2_21mer_win1_26459 26459 26479 3040 TAGAAGACCAGATTTGCTTGA 4022AGTTCGTTTAGACCAGAAGAT NC_045512.2_21mer_win1_26460 26460 26480 3041AGAAGACCAGATTTGCTTGAT 4023 TAGTTCGTTTAGACCAGAAGANC_045512.2_21mer_win1_26461 26461 26481 3042 GAAGACCAGATTTGCTTGATT 4024TTAGTTCGTTTAGACCAGAAG NC_045512.2_21mer_win1_26574 26574 26594 3043CTTGTTACCTTGGATCATTAT 4025 TATTACTAGGTTCCATTGTTCNC_045512.2_21mer_win1_26575 26575 26595 3044 TTGTTACCTTGGATCATTATC 4026CTATTACTAGGTTCCATTGTT NC_045512.2_21mer_win1_26576 26576 26596 3045TGTTACCTTGGATCATTATCC 4027 CCTATTACTAGGTTCCATTGTNC_045512.2_21mer_win1_26577 26577 26597 3046 GTTACCTTGGATCATTATCCA 4028ACCTATTACTAGGTTCCATTG NC_045512.2_21mer_win1_26578 26578 26598 3047TTACCTTGGATCATTATCCAA 4029 AACCTATTACTAGGTTCCATTNC_045512.2_21mer_win1_26579 26579 26599 3048 TACCTTGGATCATTATCCAAA 4030AAACCTATTACTAGGTTCCAT NC_045512.2_21mer_win1_26580 26580 26600 3049ACCTTGGATCATTATCCAAAG 4031 GAAACCTATTACTAGGTTCCANC_045512.2_21mer_win1_27033 27033 27053 3050 CGATGTAGTGCTTGCGAAAGA 4032AGAAAGCGTTCGTGATGTAGC NC_045512.2_21mer_win1_27034 27034 27054 3051GATGTAGTGCTTGCGAAAGAA 4033 AAGAAAGCGTTCGTGATGTAGNC_045512.2_21mer_win1_27035 27035 27055 3052 ATGTAGTGCTTGCGAAAGAAT 4034TAAGAAAGCGTTCGTGATGTA NC_045512.2_21mer_win1_27036 27036 27056 3053TGTAGTGCTTGCGAAAGAATA 4035 ATAAGAAAGCGTTCGTGATGTNC_045512.2_21mer_win1_27037 27037 27057 3054 GTAGTGCTTGCGAAAGAATAA 4036AATAAGAAAGCGTTCGTGATG NC_045512.2_21mer_win1_27038 27038 27058 3055TAGTGCTTGCGAAAGAATAAT 4037 TAATAAGAAAGCGTTCGTGATNC_045512.2_21mer_win1_27039 27039 27059 3056 AGTGCTTGCGAAAGAATAATG 4038GTAATAAGAAAGCGTTCGTGA NC_045512.2_21mer_win1_27040 27040 27060 3057GTGCTTGCGAAAGAATAATGT 4039 TGTAATAAGAAAGCGTTCGTGNC_045512.2_21mer_win1_27041 27041 27061 3058 TGCTTGCGAAAGAATAATGTT 4040TTGTAATAAGAAAGCGTTCGT NC_045512.2_21mer_win1_27042 27042 27062 3059GCTTGCGAAAGAATAATGTTT 4041 TTTGTAATAAGAAAGCGTTCGNC_045512.2_21mer_win1_27043 27043 27063 3060 CTTGCGAAAGAATAATGTTTA 4042ATTTGTAATAAGAAAGCGTTC NC_045512.2_21mer_win1_27044 27044 27064 3061TTGCGAAAGAATAATGTTTAA 4043 AATTTGTAATAAGAAAGCGTTNC_045512.2_21mer_win1_27183 27183 27203 3062 CATGTCATTCACTGTTGTCTA 4044ATCTGTTGTCACTTACTGTAC NC_045512.2_21mer_win1_27184 27184 27204 3063ATGTCATTCACTGTTGTCTAC 4045 CATCTGTTGTCACTTACTGTANC_045512.2_21mer_win1_27185 27185 27205 3064 TGTCATTCACTGTTGTCTACA 4046ACATCTGTTGTCACTTACTGT NC_045512.2_21mer_win1_27186 27186 27206 3065GTCATTCACTGTTGTCTACAA 4047 AACATCTGTTGTCACTTACTGNC_045512.2_21mer_win1_27187 27187 27207 3066 TCATTCACTGTTGTCTACAAA 4048AAACATCTGTTGTCACTTACT NC_045512.2_21mer_win1_27188 27188 27208 3067CATTCACTGTTGTCTACAAAG 4049 GAAACATCTGTTGTCACTTACNC_045512.2_21mer_win1_27189 27189 27209 3068 ATTCACTGTTGTCTACAAAGT 4050TGAAACATCTGTTGTCACTTA NC_045512.2_21mer_win1_27190 27190 27210 3069TTCACTGTTGTCTACAAAGTA 4051 ATGAAACATCTGTTGTCACTTNC_045512.2_21mer_win1_27191 27191 27211 3070 TCACTGTTGTCTACAAAGTAG 4052GATGAAACATCTGTTGTCACT NC_045512.2_21mer_win1_27192 27192 27212 3071CACTGTTGTCTACAAAGTAGA 4053 AGATGAAACATCTGTTGTCACNC_045512.2_21mer_win1_27382 27382 27402 3072 CTAATTTGCTTGTACTTTTAA 4054AATTTTCATGTTCGTTTAATC NC_045512.2_21mer_win1_27383 27383 27403 3073TAATTTGCTTGTACTTTTAAT 4055 TAATTTTCATGTTCGTTTAATNC_045512.2_21mer_win1_27384 27384 27404 3074 AATTTGCTTGTACTTTTAATA 4056ATAATTTTCATGTTCGTTTAA NC_045512.2_21mer_win1_27385 27385 27405 3075ATTTGCTTGTACTTTTAATAA 4057 AATAATTTTCATGTTCGTTTANC_045512.2_21mer_win1_27386 27386 27406 3076 TTTGCTTGTACTTTTAATAAG 4058GAATAATTTTCATGTTCGTTT NC_045512.2_21mer_win1_27387 27387 27407 3077TTGCTTGTACTTTTAATAAGA 4059 AGAATAATTTTCATGTTCGTTNC_045512.2_21mer_win1_27511 27511 27531 3078 ATGCTCCCGTTAAGTGGTAAA 4060AAATGGTGAATTGCCCTCGTA NC_045512.2_21mer_win1_27512 27512 27532 3079TGCTCCCGTTAAGTGGTAAAG 4061 GAAATGGTGAATTGCCCTCGTNC_045512.2_21mer_win1_27513 27513 27533 3080 GCTCCCGTTAAGTGGTAAAGT 4062TGAAATGGTGAATTGCCCTCG NC_045512.2_21mer_win1_27771 27771 27791 3081AATTAACTGAAGATAAACACG 4063 GCACAAATAGAAGTCAATTAANC_045512.2_21mer_win1_27772 27772 27792 3082 ATTAACTGAAGATAAACACGA 4064AGCACAAATAGAAGTCAATTA NC_045512.2_21mer_win1_27773 27773 27793 3083TTAACTGAAGATAAACACGAA 4065 AAGCACAAATAGAAGTCAATTNC_045512.2_21mer_win1_27774 27774 27794 3084 TAACTGAAGATAAACACGAAA 4066AAAGCACAAATAGAAGTCAAT NC_045512.2_21mer_win1_27775 27775 27795 3085AACTGAAGATAAACACGAAAA 4067 AAAAGCACAAATAGAAGTCAANC_045512.2_21mer_win1_27776 27776 27796 3086 ACTGAAGATAAACACGAAAAA 4068AAAAAGCACAAATAGAAGTCA NC_045512.2_21mer_win1_27777 27777 27797 3087CTGAAGATAAACACGAAAAAT 4069 TAAAAAGCACAAATAGAAGTCNC_045512.2_21mer_win1_27778 27778 27798 3088 TGAAGATAAACACGAAAAATC 4070CTAAAAAGCACAAATAGAAGT NC_045512.2_21mer_win1_27779 27779 27799 3089GAAGATAAACACGAAAAATCG 4071 GCTAAAAAGCACAAATAGAAGNC_045512.2_21mer_win1_27780 27780 27800 3090 AAGATAAACACGAAAAATCGG 4072GGCTAAAAAGCACAAATAGAA NC_045512.2_21mer_win1_27781 27781 27801 3091AGATAAACACGAAAAATCGGA 4073 AGGCTAAAAAGCACAAATAGANC_045512.2_21mer_win1_27782 27782 27802 3092 GATAAACACGAAAAATCGGAA 4074AAGGCTAAAAAGCACAAATAG NC_045512.2_21mer_win1_27783 27783 27803 3093ATAAACACGAAAAATCGGAAA 4075 AAAGGCTAAAAAGCACAAATANC_045512.2_21mer_win1_27784 27784 27804 3094 TAAACACGAAAAATCGGAAAG 4076GAAAGGCTAAAAAGCACAAAT NC_045512.2_21mer_win1_27785 27785 27805 3095AAACACGAAAAATCGGAAAGA 4077 AGAAAGGCTAAAAAGCACAAANC_045512.2_21mer_win1_27786 27786 27806 3096 AACACGAAAAATCGGAAAGAC 4078CAGAAAGGCTAAAAAGCACAA NC_045512.2_21mer_win1_27787 27787 27807 3097ACACGAAAAATCGGAAAGACG 4079 GCAGAAAGGCTAAAAAGCACANC_045512.2_21mer_win1_27788 27788 27808 3098 CACGAAAAATCGGAAAGACGA 4080AGCAGAAAGGCTAAAAAGCAC NC_045512.2_21mer_win1_27789 27789 27809 3099ACGAAAAATCGGAAAGACGAT 4081 TAGCAGAAAGGCTAAAAAGCANC_045512.2_21mer_win1_27790 27790 27810 3100 CGAAAAATCGGAAAGACGATA 4082ATAGCAGAAAGGCTAAAAAGC NC_045512.2_21mer_win1_27791 27791 27811 3101GAAAAATCGGAAAGACGATAA 4083 AATAGCAGAAAGGCTAAAAAGNC_045512.2_21mer_win1_27792 27792 27812 3102 AAAAATCGGAAAGACGATAAG 4084GAATAGCAGAAAGGCTAAAAA NC_045512.2_21mer_win1_27793 27793 27813 3103AAAATCGGAAAGACGATAAGG 4085 GGAATAGCAGAAAGGCTAAAANC_045512.2_21mer_win1_27794 27794 27814 3104 AAATCGGAAAGACGATAAGGA 4086AGGAATAGCAGAAAGGCTAAA NC_045512.2_21mer_win1_27795 27795 27815 3105AATCGGAAAGACGATAAGGAA 4087 AAGGAATAGCAGAAAGGCTAANC_045512.2_21mer_win1_27796 27796 27816 3106 ATCGGAAAGACGATAAGGAAC 4088CAAGGAATAGCAGAAAGGCTA NC_045512.2_21mer_win1_27797 27797 27817 3107TCGGAAAGACGATAAGGAACA 4089 ACAAGGAATAGCAGAAAGGCTNC_045512.2_21mer_win1_27798 27798 27818 3108 CGGAAAGACGATAAGGAACAA 4090AACAAGGAATAGCAGAAAGGC NC_045512.2_21mer_win1_28270 28270 28290 3109ATTTTACAGACTATTACCTGG 4091 GGTCCATTATCAGACATTTTANC_045512.2_21mer_win1_28271 28271 28291 3110 TTTTACAGACTATTACCTGGG 4092GGGTCCATTATCAGACATTTT NC_045512.2_21mer_win1_28272 28272 28292 3111TTTACAGACTATTACCTGGGG 4093 GGGGTCCATTATCAGACATTTNC_045512.2_21mer_win1_28273 28273 28293 3112 TTACAGACTATTACCTGGGGT 4094TGGGGTCCATTATCAGACATT NC_045512.2_21mer_win1_28274 28274 28294 3113TACAGACTATTACCTGGGGTT 4095 TTGGGGTCCATTATCAGACATNC_045512.2_21mer_win1_28275 28275 28295 3114 ACAGACTATTACCTGGGGTTT 4096TTTGGGGTCCATTATCAGACA NC_045512.2_21mer_win1_28276 28276 28296 3115CAGACTATTACCTGGGGTTTT 4097 TTTTGGGGTCCATTATCAGACNC_045512.2_21mer_win1_28397 28397 28417 3116 GGGGTTCCAAATGGGTTATTA 4098ATTATTGGGTAAACCTTGGGG NC_045512.2_21mer_win1_28398 28398 28418 3117GGGTTCCAAATGGGTTATTAT 4099 TATTATTGGGTAAACCTTGGGNC_045512.2_21mer_win1_28399 28399 28419 3118 GGTTCCAAATGGGTTATTATG 4100GTATTATTGGGTAAACCTTGG NC_045512.2_21mer_win1_28400 28400 28420 3119GTTCCAAATGGGTTATTATGA 4101 AGTATTATTGGGTAAACCTTGNC_045512.2_21mer_win1_28401 28401 28421 3120 TTCCAAATGGGTTATTATGAC 4102CAGTATTATTGGGTAAACCTT NC_045512.2_21mer_win1_28402 28402 28422 3121TCCAAATGGGTTATTATGACG 4103 GCAGTATTATTGGGTAAACCTNC_045512.2_21mer_win1_28403 28403 28423 3122 CCAAATGGGTTATTATGACGC 4104CGCAGTATTATTGGGTAAACC NC_045512.2_21mer_win1_28404 28404 28424 3123CAAATGGGTTATTATGACGCA 4105 ACGCAGTATTATTGGGTAAACNC_045512.2_21mer_win1_28405 28405 28425 3124 AAATGGGTTATTATGACGCAG 4106GACGCAGTATTATTGGGTAAA NC_045512.2_21mer_win1_28406 28406 28426 3125AATGGGTTATTATGACGCAGA 4107 AGACGCAGTATTATTGGGTAANC_045512.2_21mer_win1_28407 28407 28427 3126 ATGGGTTATTATGACGCAGAA 4108AAGACGCAGTATTATTGGGTA NC_045512.2_21mer_win1_28408 28408 28428 3127TGGGTTATTATGACGCAGAAC 4109 CAAGACGCAGTATTATTGGGTNC_045512.2_21mer_win1_28409 28409 28429 3128 GGGTTATTATGACGCAGAACC 4110CCAAGACGCAGTATTATTGGG NC_045512.2_21mer_win1_28410 28410 28430 3129GGTTATTATGACGCAGAACCA 4111 ACCAAGACGCAGTATTATTGGNC_045512.2_21mer_win1_28411 28411 28431 3130 GTTATTATGACGCAGAACCAA 4112AACCAAGACGCAGTATTATTG NC_045512.2_21mer_win1_28412 28412 28432 3131TTATTATGACGCAGAACCAAG 4113 GAACCAAGACGCAGTATTATTNC_045512.2_21mer_win1_28413 28413 28433 3132 TATTATGACGCAGAACCAAGT 4114TGAACCAAGACGCAGTATTAT NC_045512.2_21mer_win1_28414 28414 28434 3133ATTATGACGCAGAACCAAGTG 4115 GTGAACCAAGACGCAGTATTANC_045512.2_21mer_win1_28513 28513 28533 3134 TCTACTGGTTTAACCGATGAT 4116TAGTAGCCAATTTGGTCATCT NC_045512.2_21mer_win1_28514 28514 28534 3135CTACTGGTTTAACCGATGATG 4117 GTAGTAGCCAATTTGGTCATCNC_045512.2_21mer_win1_28515 28515 28535 3136 TACTGGTTTAACCGATGATGG 4118GGTAGTAGCCAATTTGGTCAT NC_045512.2_21mer_win1_28516 28516 28536 3137ACTGGTTTAACCGATGATGGC 4119 CGGTAGTAGCCAATTTGGTCANC_045512.2_21mer_win1_28517 28517 28537 3138 CTGGTTTAACCGATGATGGCT 4120TCGGTAGTAGCCAATTTGGTC NC_045512.2_21mer_win1_28518 28518 28538 3139TGGTTTAACCGATGATGGCTT 4121 TTCGGTAGTAGCCAATTTGGTNC_045512.2_21mer_win1_28519 28519 28539 3140 GGTTTAACCGATGATGGCTTC 4122CTTCGGTAGTAGCCAATTTGG NC_045512.2_21mer_win1_28520 28520 28540 3141GTTTAACCGATGATGGCTTCT 4123 TCTTCGGTAGTAGCCAATTTGNC_045512.2_21mer_win1_28521 28521 28541 3142 TTTAACCGATGATGGCTTCTC 4124CTCTTCGGTAGTAGCCAATTT NC_045512.2_21mer_win1_28522 28522 28542 3143TTAACCGATGATGGCTTCTCG 4125 GCTCTTCGGTAGTAGCCAATTNC_045512.2_21mer_win1_28523 28523 28543 3144 TAACCGATGATGGCTTCTCGA 4126AGCTCTTCGGTAGTAGCCAAT NC_045512.2_21mer_win1_28524 28524 28544 3145AACCGATGATGGCTTCTCGAT 4127 TAGCTCTTCGGTAGTAGCCAANC_045512.2_21mer_win1_28525 28525 28545 3146 ACCGATGATGGCTTCTCGATG 4128GTAGCTCTTCGGTAGTAGCCA NC_045512.2_21mer_win1_28526 28526 28546 3147CCGATGATGGCTTCTCGATGG 4129 GGTAGCTCTTCGGTAGTAGCCNC_045512.2_21mer_win1_28706 28706 28726 3148 GTGTAACCGTGGGCGTTAGGA 4130AGGATTGCGGGTGCCAATGTG NC_045512.2_21mer_win1_28744 28744 28764 3149GCACGATGTTGAAGGAGTTCC 4131 CCTTGAGGAAGTTGTAGCACGNC_045512.2_21mer_win1_28745 28745 28765 3150 CACGATGTTGAAGGAGTTCCT 4132TCCTTGAGGAAGTTGTAGCAC NC_045512.2_21mer_win1_28746 28746 28766 3151ACGATGTTGAAGGAGTTCCTT 4133 TTCCTTGAGGAAGTTGTAGCANC_045512.2_21mer_win1_28747 28747 28767 3152 CGATGTTGAAGGAGTTCCTTG 4134GTTCCTTGAGGAAGTTGTAGC NC_045512.2_21mer_win1_28748 28748 28768 3153GATGTTGAAGGAGTTCCTTGT 4135 TGTTCCTTGAGGAAGTTGTAGNC_045512.2_21mer_win1_28749 28749 28769 3154 ATGTTGAAGGAGTTCCTTGTT 4136TTGTTCCTTGAGGAAGTTGTA NC_045512.2_21mer_win1_28750 28750 28770 3155TGTTGAAGGAGTTCCTTGTTG 4137 GTTGTTCCTTGAGGAAGTTGTNC_045512.2_21mer_win1_28751 28751 28771 3156 GTTGAAGGAGTTCCTTGTTGT 4138TGTTGTTCCTTGAGGAAGTTG NC_045512.2_21mer_win1_28752 28752 28772 3157TTGAAGGAGTTCCTTGTTGTA 4139 ATGTTGTTCCTTGAGGAAGTTNC_045512.2_21mer_win1_28753 28753 28773 3158 TGAAGGAGTTCCTTGTTGTAA 4140AATGTTGTTCCTTGAGGAAGT NC_045512.2_21mer_win1_28754 28754 28774 3159GAAGGAGTTCCTTGTTGTAAC 4141 CAATGTTGTTCCTTGAGGAAGNC_045512.2_21mer_win1_28755 28755 28775 3160 AAGGAGTTCCTTGTTGTAACG 4142GCAATGTTGTTCCTTGAGGAA NC_045512.2_21mer_win1_28756 28756 28776 3161AGGAGTTCCTTGTTGTAACGG 4143 GGCAATGTTGTTCCTTGAGGANC_045512.2_21mer_win1_28757 28757 28777 3162 GGAGTTCCTTGTTGTAACGGT 4144TGGCAATGTTGTTCCTTGAGG NC_045512.2_21mer_win1_28758 28758 28778 3163GAGTTCCTTGTTGTAACGGTT 4145 TTGGCAATGTTGTTCCTTGAGNC_045512.2_21mer_win1_28759 28759 28779 3164 AGTTCCTTGTTGTAACGGTTT 4146TTTGGCAATGTTGTTCCTTGA NC_045512.2_21mer_win1_28760 28760 28780 3165GTTCCTTGTTGTAACGGTTTT 4147 TTTTGGCAATGTTGTTCCTTGNC_045512.2_21mer_win1_28761 28761 28781 3166 TTCCTTGTTGTAACGGTTTTC 4148CTTTTGGCAATGTTGTTCCTT NC_045512.2_21mer_win1_28762 28762 28782 3167TCCTTGTTGTAACGGTTTTCC 4149 CCTTTTGGCAATGTTGTTCCTNC_045512.2_21mer_win1_28763 28763 28783 3168 CCTTGTTGTAACGGTTTTCCG 4150GCCTTTTGGCAATGTTGTTCC NC_045512.2_21mer_win1_28764 28764 28784 3169CTTGTTGTAACGGTTTTCCGA 4151 AGCCTTTTGGCAATGTTGTTCNC_045512.2_21mer_win1_28765 28765 28785 3170 TTGTTGTAACGGTTTTCCGAA 4152AAGCCTTTTGGCAATGTTGTT NC_045512.2_21mer_win1_28766 28766 28786 3171TGTTGTAACGGTTTTCCGAAG 4153 GAAGCCTTTTGGCAATGTTGTNC_045512.2_21mer_win1_28767 28767 28787 3172 GTTGTAACGGTTTTCCGAAGA 4154AGAAGCCTTTTGGCAATGTTG NC_045512.2_21mer_win1_28768 28768 28788 3173TTGTAACGGTTTTCCGAAGAT 4155 TAGAAGCCTTTTGGCAATGTTNC_045512.2_21mer_win1_28769 28769 28789 3174 TGTAACGGTTTTCCGAAGATG 4156GTAGAAGCCTTTTGGCAATGT NC_045512.2_21mer_win1_28770 28770 28790 3175GTAACGGTTTTCCGAAGATGC 4157 CGTAGAAGCCTTTTGGCAATGNC_045512.2_21mer_win1_28771 28771 28791 3176 TAACGGTTTTCCGAAGATGCG 4158GCGTAGAAGCCTTTTGGCAAT NC_045512.2_21mer_win1_28772 28772 28792 3177AACGGTTTTCCGAAGATGCGT 4159 TGCGTAGAAGCCTTTTGGCAANC_045512.2_21mer_win1_28773 28773 28793 3178 ACGGTTTTCCGAAGATGCGTC 4160CTGCGTAGAAGCCTTTTGGCA NC_045512.2_21mer_win1_28774 28774 28794 3179CGGTTTTCCGAAGATGCGTCT 4161 TCTGCGTAGAAGCCTTTTGGCNC_045512.2_21mer_win1_28799 28799 28819 3180 TCGTCTCCGCCGTCAGTTCGG 4162GGCTTGACTGCCGCCTCTGCT NC_045512.2_21mer_win1_28800 28800 28820 3181CGTCTCCGCCGTCAGTTCGGA 4163 AGGCTTGACTGCCGCCTCTGCNC_045512.2_21mer_win1_28801 28801 28821 3182 GTCTCCGCCGTCAGTTCGGAG 4164GAGGCTTGACTGCCGCCTCTG NC_045512.2_21mer_win1_28802 28802 28822 3183TCTCCGCCGTCAGTTCGGAGA 4165 AGAGGCTTGACTGCCGCCTCTNC_045512.2_21mer_win1_28803 28803 28823 3184 CTCCGCCGTCAGTTCGGAGAA 4166AAGAGGCTTGACTGCCGCCTC NC_045512.2_21mer_win1_28804 28804 28824 3185TCCGCCGTCAGTTCGGAGAAG 4167 GAAGAGGCTTGACTGCCGCCTNC_045512.2_21mer_win1_28805 28805 28825 3186 CCGCCGTCAGTTCGGAGAAGA 4168AGAAGAGGCTTGACTGCCGCC NC_045512.2_21mer_win1_28806 28806 28826 3187CGCCGTCAGTTCGGAGAAGAG 4169 GAGAAGAGGCTTGACTGCCGCNC_045512.2_21mer_win1_28807 28807 28827 3188 GCCGTCAGTTCGGAGAAGAGC 4170CGAGAAGAGGCTTGACTGCCG NC_045512.2_21mer_win1_28946 28946 28966 3189CTGTCTAACTTGGTCGAACTC 4171 CTCAAGCTGGTTCAATCTGTCNC_045512.2_21mer_win1_28947 28947 28967 3190 TGTCTAACTTGGTCGAACTCT 4172TCTCAAGCTGGTTCAATCTGT NC_045512.2_21mer_win1_28948 28948 28968 3191GTCTAACTTGGTCGAACTCTC 4173 CTCTCAAGCTGGTTCAATCTGNC_045512.2_21mer_win1_28949 28949 28969 3192 TCTAACTTGGTCGAACTCTCG 4174GCTCTCAAGCTGGTTCAATCT NC_045512.2_21mer_win1_28950 28950 28970 3193CTAACTTGGTCGAACTCTCGT 4175 TGCTCTCAAGCTGGTTCAATCNC_045512.2_21mer_win1_28951 28951 28971 3194 TAACTTGGTCGAACTCTCGTT 4176TTGCTCTCAAGCTGGTTCAAT NC_045512.2_21mer_win1_28952 28952 28972 3195AACTTGGTCGAACTCTCGTTT 4177 TTTGCTCTCAAGCTGGTTCAANC_045512.2_21mer_win1_28976 28976 28996 3196 AGACCATTTCCGGTTGTTGTT 4178TTGTTGTTGGCCTTTACCAGA NC_045512.2_21mer_win1_28977 28977 28997 3197GACCATTTCCGGTTGTTGTTG 4179 GTTGTTGTTGGCCTTTACCAGNC_045512.2_21mer_win1_28978 28978 28998 3198 ACCATTTCCGGTTGTTGTTGT 4180TGTTGTTGTTGGCCTTTACCA NC_045512.2_21mer_win1_28979 28979 28999 3199CCATTTCCGGTTGTTGTTGTT 4181 TTGTTGTTGTTGGCCTTTACCNC_045512.2_21mer_win1_28980 28980 29000 3200 CATTTCCGGTTGTTGTTGTTC 4182CTTGTTGTTGTTGGCCTTTAC NC_045512.2_21mer_win1_28981 28981 29001 3201ATTTCCGGTTGTTGTTGTTCC 4183 CCTTGTTGTTGTTGGCCTTTANC_045512.2_21mer_win1_28982 28982 29002 3202 TTTCCGGTTGTTGTTGTTCCG 4184GCCTTGTTGTTGTTGGCCTTT NC_045512.2_21mer_win1_28983 28983 29003 3203TTCCGGTTGTTGTTGTTCCGG 4185 GGCCTTGTTGTTGTTGGCCTTNC_045512.2_21mer_win1_28984 28984 29004 3204 TCCGGTTGTTGTTGTTCCGGT 4186TGGCCTTGTTGTTGTTGGCCT NC_045512.2_21mer_win1_28985 28985 29005 3205CCGGTTGTTGTTGTTCCGGTT 4187 TTGGCCTTGTTGTTGTTGGCCNC_045512.2_21mer_win1_28986 28986 29006 3206 CGGTTGTTGTTGTTCCGGTTT 4188TTTGGCCTTGTTGTTGTTGGC NC_045512.2_21mer_win1_28987 28987 29007 3207GGTTGTTGTTGTTCCGGTTTG 4189 GTTTGGCCTTGTTGTTGTTGGNC_045512.2_21mer_win1_28988 28988 29008 3208 GTTGTTGTTGTTCCGGTTTGA 4190AGTTTGGCCTTGTTGTTGTTG NC_045512.2_21mer_win1_28989 28989 29009 3209TTGTTGTTGTTCCGGTTTGAC 4191 CAGTTTGGCCTTGTTGTTGTTNC_045512.2_21mer_win1_28990 28990 29010 3210 TGTTGTTGTTCCGGTTTGACA 4192ACAGTTTGGCCTTGTTGTTGT NC_045512.2_21mer_win1_28991 28991 29011 3211GTTGTTGTTCCGGTTTGACAG 4193 GACAGTTTGGCCTTGTTGTTGNC_045512.2_21mer_win1_28992 28992 29012 3212 TTGTTGTTCCGGTTTGACAGT 4194TGACAGTTTGGCCTTGTTGTT NC_045512.2_21mer_win1_28993 28993 29013 3213TGTTGTTCCGGTTTGACAGTG 4195 GTGACAGTTTGGCCTTGTTGTNC_045512.2_21mer_win1_28994 28994 29014 3214 GTTGTTCCGGTTTGACAGTGA 4196AGTGACAGTTTGGCCTTGTTG NC_045512.2_21mer_win1_28995 28995 29015 3215TTGTTCCGGTTTGACAGTGAT 4197 TAGTGACAGTTTGGCCTTGTTNC_045512.2_21mer_win1_28996 28996 29016 3216 TGTTCCGGTTTGACAGTGATT 4198TTAGTGACAGTTTGGCCTTGT NC_045512.2_21mer_win1_28997 28997 29017 3217GTTCCGGTTTGACAGTGATTC 4199 CTTAGTGACAGTTTGGCCTTGNC_045512.2_21mer_win1_28998 28998 29018 3218 TTCCGGTTTGACAGTGATTCT 4200TCTTAGTGACAGTTTGGCCTT NC_045512.2_21mer_win1_28999 28999 29019 3219TCCGGTTTGACAGTGATTCTT 4201 TTCTTAGTGACAGTTTGGCCTNC_045512.2_21mer_win1_29000 29000 29020 3220 CCGGTTTGACAGTGATTCTTT 4202TTTCTTAGTGACAGTTTGGCC NC_045512.2_21mer_win1_29001 29001 29021 3221CGGTTTGACAGTGATTCTTTA 4203 ATTTCTTAGTGACAGTTTGGCNC_045512.2_21mer_win1_29002 29002 29022 3222 GGTTTGACAGTGATTCTTTAG 4204GATTTCTTAGTGACAGTTTGG NC_045512.2_21mer_win1_29003 29003 29023 3223GTTTGACAGTGATTCTTTAGA 4205 AGATTTCTTAGTGACAGTTTGNC_045512.2_21mer_win1_29004 29004 29024 3224 TTTGACAGTGATTCTTTAGAC 4206CAGATTTCTTAGTGACAGTTT NC_045512.2_21mer_win1_29005 29005 29025 3225TTGACAGTGATTCTTTAGACG 4207 GCAGATTTCTTAGTGACAGTTNC_045512.2_21mer_win1_29006 29006 29026 3226 TGACAGTGATTCTTTAGACGA 4208AGCAGATTTCTTAGTGACAGT NC_045512.2_21mer_win1_29007 29007 29027 3227GACAGTGATTCTTTAGACGAC 4209 CAGCAGATTTCTTAGTGACAGNC_045512.2_21mer_win1_29008 29008 29028 3228 ACAGTGATTCTTTAGACGACG 4210GCAGCAGATTTCTTAGTGACA NC_045512.2_21mer_win1_29009 29009 29029 3229CAGTGATTCTTTAGACGACGA 4211 AGCAGCAGATTTCTTAGTGACNC_045512.2_21mer_win1_29010 29010 29030 3230 AGTGATTCTTTAGACGACGAC 4212CAGCAGCAGATTTCTTAGTGA NC_045512.2_21mer_win1_29011 29011 29031 3231GTGATTCTTTAGACGACGACT 4213 TCAGCAGCAGATTTCTTAGTGNC_045512.2_21mer_win1_29012 29012 29032 3232 TGATTCTTTAGACGACGACTC 4214CTCAGCAGCAGATTTCTTAGT NC_045512.2_21mer_win1_29013 29013 29033 3233GATTCTTTAGACGACGACTCC 4215 CCTCAGCAGCAGATTTCTTAGNC_045512.2_21mer_win1_29014 29014 29034 3234 ATTCTTTAGACGACGACTCCG 4216GCCTCAGCAGCAGATTTCTTA NC_045512.2_21mer_win1_29144 29144 29164 3235GATTAGTCTGTTCCTTGACTA 4217 ATCAGTTCCTTGTCTGATTAGNC_045512.2_21mer_win1_29145 29145 29165 3236 ATTAGTCTGTTCCTTGACTAA 4218AATCAGTTCCTTGTCTGATTA NC_045512.2_21mer_win1_29146 29146 29166 3237TTAGTCTGTTCCTTGACTAAT 4219 TAATCAGTTCCTTGTCTGATTNC_045512.2_21mer_win1_29147 29147 29167 3238 TAGTCTGTTCCTTGACTAATG 4220GTAATCAGTTCCTTGTCTGAT NC_045512.2_21mer_win1_29148 29148 29168 3239AGTCTGTTCCTTGACTAATGT 4221 TGTAATCAGTTCCTTGTCTGANC_045512.2_21mer_win1_29149 29149 29169 3240 GTCTGTTCCTTGACTAATGTT 4222TTGTAATCAGTTCCTTGTCTG NC_045512.2_21mer_win1_29150 29150 29170 3241TCTGTTCCTTGACTAATGTTT 4223 TTTGTAATCAGTTCCTTGTCTNC_045512.2_21mer_win1_29151 29151 29171 3242 CTGTTCCTTGACTAATGTTTG 4224GTTTGTAATCAGTTCCTTGTC NC_045512.2_21mer_win1_29152 29152 29172 3243TGTTCCTTGACTAATGTTTGT 4225 TGTTTGTAATCAGTTCCTTGTNC_045512.2_21mer_win1_29174 29174 29194 3244 ACCGGCGTTTAACGTGTTAAA 4226AAATTGTGCAATTTGCGGCCA NC_045512.2_21mer_win1_29175 29175 29195 3245CCGGCGTTTAACGTGTTAAAC 4227 CAAATTGTGCAATTTGCGGCCNC_045512.2_21mer_win1_29176 29176 29196 3246 CGGCGTTTAACGTGTTAAACG 4228GCAAATTGTGCAATTTGCGGC NC_045512.2_21mer_win1_29228 29228 29248 3247GCGTAACCGTACCTTCAGTGT 4229 TGTGACTTCCATGCCAATGCGNC_045512.2_21mer_win1_29229 29229 29249 3248 CGTAACCGTACCTTCAGTGTG 4230GTGTGACTTCCATGCCAATGC NC_045512.2_21mer_win1_29230 29230 29250 3249GTAACCGTACCTTCAGTGTGG 4231 GGTGTGACTTCCATGCCAATGNC_045512.2_21mer_win1_29231 29231 29251 3250 TAACCGTACCTTCAGTGTGGA 4232AGGTGTGACTTCCATGCCAAT NC_045512.2_21mer_win1_29232 29232 29252 3251AACCGTACCTTCAGTGTGGAA 4233 AAGGTGTGACTTCCATGCCAANC_045512.2_21mer_win1_29233 29233 29253 3252 ACCGTACCTTCAGTGTGGAAG 4234GAAGGTGTGACTTCCATGCCA NC_045512.2_21mer_win1_29234 29234 29254 3253CCGTACCTTCAGTGTGGAAGC 4235 CGAAGGTGTGACTTCCATGCCNC_045512.2_21mer_win1_29235 29235 29255 3254 CGTACCTTCAGTGTGGAAGCC 4236CCGAAGGTGTGACTTCCATGC NC_045512.2_21mer_win1_29236 29236 29256 3255GTACCTTCAGTGTGGAAGCCC 4237 CCCGAAGGTGTGACTTCCATGNC_045512.2_21mer_win1_29237 29237 29257 3256 TACCTTCAGTGTGGAAGCCCT 4238TCCCGAAGGTGTGACTTCCAT NC_045512.2_21mer_win1_29238 29238 29258 3257ACCTTCAGTGTGGAAGCCCTT 4239 TTCCCGAAGGTGTGACTTCCANC_045512.2_21mer_win1_29239 29239 29259 3258 CCTTCAGTGTGGAAGCCCTTG 4240GTTCCCGAAGGTGTGACTTCC NC_045512.2_21mer_win1_29285 29285 29305 3259TTTAACCTACTGTTTCTAGGT 4241 TGGATCTTTGTCATCCAATTTNC_045512.2_21mer_win1_29342 29342 29362 3260 TAACTGCGTATGTTTTGTAAG 4242GAATGTTTTGTATGCGTCAAT NC_045512.2_21mer_win1_29343 29343 29363 3261AACTGCGTATGTTTTGTAAGG 4243 GGAATGTTTTGTATGCGTCAANC_045512.2_21mer_win1_29344 29344 29364 3262 ACTGCGTATGTTTTGTAAGGG 4244GGGAATGTTTTGTATGCGTCA NC_045512.2_21mer_win1_29345 29345 29365 3263CTGCGTATGTTTTGTAAGGGT 4245 TGGGAATGTTTTGTATGCGTCNC_045512.2_21mer_win1_29346 29346 29366 3264 TGCGTATGTTTTGTAAGGGTG 4246GTGGGAATGTTTTGTATGCGT NC_045512.2_21mer_win1_29347 29347 29367 3265GCGTATGTTTTGTAAGGGTGG 4247 GGTGGGAATGTTTTGTATGCGNC_045512.2_21mer_win1_29348 29348 29368 3266 CGTATGTTTTGTAAGGGTGGT 4248TGGTGGGAATGTTTTGTATGC NC_045512.2_21mer_win1_29349 29349 29369 3267GTATGTTTTGTAAGGGTGGTT 4249 TTGGTGGGAATGTTTTGTATGNC_045512.2_21mer_win1_29350 29350 29370 3268 TATGTTTTGTAAGGGTGGTTG 4250GTTGGTGGGAATGTTTTGTAT NC_045512.2_21mer_win1_29351 29351 29371 3269ATGTTTTGTAAGGGTGGTTGT 4251 TGTTGGTGGGAATGTTTTGTANC_045512.2_21mer_win1_29352 29352 29372 3270 TGTTTTGTAAGGGTGGTTGTC 4252CTGTTGGTGGGAATGTTTTGT NC_045512.2_21mer_win1_29353 29353 29373 3271GTTTTGTAAGGGTGGTTGTCT 4253 TCTGTTGGTGGGAATGTTTTGNC_045512.2_21mer_win1_29354 29354 29374 3272 TTTTGTAAGGGTGGTTGTCTC 4254CTCTGTTGGTGGGAATGTTTT NC_045512.2_21mer_win1_29355 29355 29375 3273TTTGTAAGGGTGGTTGTCTCG 4255 GCTCTGTTGGTGGGAATGTTTNC_045512.2_21mer_win1_29356 29356 29376 3274 TTGTAAGGGTGGTTGTCTCGG 4256GGCTCTGTTGGTGGGAATGTT NC_045512.2_21mer_win1_29357 29357 29377 3275TGTAAGGGTGGTTGTCTCGGA 4257 AGGCTCTGTTGGTGGGAATGTNC_045512.2_21mer_win1_29358 29358 29378 3276 GTAAGGGTGGTTGTCTCGGAT 4258TAGGCTCTGTTGGTGGGAATG NC_045512.2_21mer_win1_29359 29359 29379 3277TAAGGGTGGTTGTCTCGGATT 4259 TTAGGCTCTGTTGGTGGGAATNC_045512.2_21mer_win1_29360 29360 29380 3278 AAGGGTGGTTGTCTCGGATTT 4260TTTAGGCTCTGTTGGTGGGAA NC_045512.2_2lmer_win1_29361 29361 29381 3279AGGGTGGTTGTCTCGGATTTT 4261 TTTTAGGCTCTGTTGGTGGGANC_045512.2_21mer_win1_29362 29362 29382 3280 GGGTGGTTGTCTCGGATTTTT 4262TTTTTAGGCTCTGTTGGTGGG NC_045512.2_21mer_win1_29363 29363 29383 3281GGTGGTTGTCTCGGATTTTTC 4263 CTTTTTAGGCTCTGTTGGTGGNC_045512.2_21mer_win1_29364 29364 29384 3282 GTGGTTGTCTCGGATTTTTCC 4264CCTTTTTAGGCTCTGTTGGTG NC_045512.2_21mer_win1_29365 29365 29385 3283TGGTTGTCTCGGATTTTTCCT 4265 TCCTTTTTAGGCTCTGTTGGTNC_045512.2_21mer_win1_29366 29366 29386 3284 GGTTGTCTCGGATTTTTCCTG 4266GTCCTTTTTAGGCTCTGTTGG NC_045512.2_21mer_win1_29367 29367 29387 3285GTTGTCTCGGATTTTTCCTGT 4267 TGTCCTTTTTAGGCTCTGTTGNC_045512.2_21mer_win1_29368 29368 29388 3286 TTGTCTCGGATTTTTCCTGTT 4268TTGTCCTTTTTAGGCTCTGTT NC_045512.2_21mer_win1_29369 29369 29389 3287TGTCTCGGATTTTTCCTGTTT 4269 TTTGTCCTTTTTAGGCTCTGTNC_045512.2_21mer_win1_29370 29370 29390 3288 GTCTCGGATTTTTCCTGTTTT 4270TTTTGTCCTTTTTAGGCTCTG NC_045512.2_2lmer_win1_29371 29371 29391 3289TCTCGGATTTTTCCTGTTTTT 4271 TTTTTGTCCTTTTTAGGCTCTNC_045512.2_21mer_win1_29372 29372 29392 3290 CTCGGATTTTTCCTGTTTTTC 4272CTTTTTGTCCTTTTTAGGCTC NC_045512.2_21mer_win1_29373 29373 29393 3291TCGGATTTTTCCTGTTTTTCT 4273 TCTTTTTGTCCTTTTTAGGCTNC_045512.2_21mer_win1_29374 29374 29394 3292 CGGATTTTTCCTGTTTTTCTT 4274TTCTTTTTGTCCTTTTTAGGC NC_045512.2_21mer_win1_29543 29543 29563 3293CTGGTGTGTTCCGTCTACCCG 4275 GCCCATCTGCCTTGTGTGGTCNC_045512.2_21mer_win1_29544 29544 29564 3294 TGGTGTGTTCCGTCTACCCGA 4276AGCCCATCTGCCTTGTGTGGT NC_045512.2_21mer_win1_29545 29545 29565 3295GGTGTGTTCCGTCTACCCGAT 4277 TAGCCCATCTGCCTTGTGTGGNC_045512.2_21mer_win1_29546 29546 29566 3296 GTGTGTTCCGTCTACCCGATA 4278ATAGCCCATCTGCCTTGTGTG NC_045512.2_21mer_win1_29598 29598 29618 3297TATCAGATGAGAACACGTCTT 4279 TTCTGCACAAGAGTAGACTATNC_045512.2_21mer_win1_29599 29599 29619 3298 ATCAGATGAGAACACGTCTTA 4280ATTCTGCACAAGAGTAGACTA NC_045512.2_21mer_win1_29600 29600 29620 3299TCAGATGAGAACACGTCTTAC 4281 CATTCTGCACAAGAGTAGACTNC_045512.2_21mer_win1_29601 29601 29621 3300 CAGATGAGAACACGTCTTACT 4282TCATTCTGCACAAGAGTAGAC NC_045512.2_21mer_win1_29602 29602 29622 3301AGATGAGAACACGTCTTACTT 4283 TTCATTCTGCACAAGAGTAGANC_045512.2_21mer_win1_29603 29603 29623 3302 GATGAGAACACGTCTTACTTA 4284ATTCATTCTGCACAAGAGTAG NC_045512.2_21mer_win1_29604 29604 29624 3303ATGAGAACACGTCTTACTTAA 4285 AATTCATTCTGCACAAGAGTANC_045512.2_21mer_win1_29605 29605 29625 3304 TGAGAACACGTCTTACTTAAG 4286GAATTCATTCTGCACAAGAGT NC_045512.2_21mer_win1_29606 29606 29626 3305GAGAACACGTCTTACTTAAGA 4287 AGAATTCATTCTGCACAAGAGNC_045512.2_21mer_win1_29607 29607 29627 3306 AGAACACGTCTTACTTAAGAG 4288GAGAATTCATTCTGCACAAGA NC_045512.2_21mer_win1_29608 29608 29628 3307GAACACGTCTTACTTAAGAGC 4289 CGAGAATTCATTCTGCACAAGNC_045512.2_21mer_win1_29609 29609 29629 3308 AACACGTCTTACTTAAGAGCA 4290ACGAGAATTCATTCTGCACAA NC_045512.2_21mer_win1_29610 29610 29630 3309ACACGTCTTACTTAAGAGCAT 4291 TACGAGAATTCATTCTGCACANC_045512.2_21mer_win1_29652 29652 29672 3310 ATCAATTGAAATTAGAGTGTA 4292ATGTGAGATTAAAGTTAACTA NC_045512.2_21mer_win1_29653 29653 29673 3311TCAATTGAAATTAGAGTGTAT 4293 TATGTGAGATTAAAGTTAACTNC_045512.2_21mer_win1_29654 29654 29674 3312 CAATTGAAATTAGAGTGTATC 4294CTATGTGAGATTAAAGTTAAC NC_045512.2_21mer_win1_29655 29655 29675 3313AATTGAAATTAGAGTGTATCG 4295 GCTATGTGAGATTAAAGTTAANC_045512.2_21mer_win1_29656 29656 29676 3314 ATTGAAATTAGAGTGTATCGT 4296TGCTATGTGAGATTAAAGTTA NC_045512.2_21mer_win1_29657 29657 29677 3315TTGAAATTAGAGTGTATCGTT 4297 TTGCTATGTGAGATTAAAGTTNC_045512.2_21mer_win1_29658 29658 29678 3316 TGAAATTAGAGTGTATCGTTA 4298ATTGCTATGTGAGATTAAAGT NC_045512.2_21mer_win1_29659 29659 29679 3317GAAATTAGAGTGTATCGTTAG 4299 GATTGCTATGTGAGATTAAAGNC_045512.2_21mer_win1_29660 29660 29680 3318 AAATTAGAGTGTATCGTTAGA 4300AGATTGCTATGTGAGATTAAA NC_045512.2_21mer_win1_29661 29661 29681 3319AATTAGAGTGTATCGTTAGAA 4301 AAGATTGCTATGTGAGATTAANC_045512.2_21mer_win1_29662 29662 29682 3320 ATTAGAGTGTATCGTTAGAAA 4302AAAGATTGCTATGTGAGATTA NC_045512.2_21mer_win1_29663 29663 29683 3321TTAGAGTGTATCGTTAGAAAT 4303 TAAAGATTGCTATGTGAGATTNC_045512.2_21mer_win1_29664 29664 29684 3322 TAGAGTGTATCGTTAGAAATT 4304TTAAAGATTGCTATGTGAGAT NC_045512.2_21mer_win1_29665 29665 29685 3323AGAGTGTATCGTTAGAAATTA 4305 ATTAAAGATTGCTATGTGAGANC_045512.2_21mer_win1_29666 29666 29686 3324 GAGTGTATCGTTAGAAATTAG 4306GATTAAAGATTGCTATGTGAG NC_045512.2_21mer_win1_29667 29667 29687 3325AGTGTATCGTTAGAAATTAGT 4307 TGATTAAAGATTGCTATGTGANC_045512.2_21mer_win1_29689 29689 29709 3326 ACACATTGTAATCCCTCCTGA 4308AGTCCTCCCTAATGTTACACA NC_045512.2_21mer_win1_29690 29690 29710 3327CACATTGTAATCCCTCCTGAA 4309 AAGTCCTCCCTAATGTTACACNC_045512.2_21mer_win1_29691 29691 29711 3328 ACATTGTAATCCCTCCTGAAC 4310CAAGTCCTCCCTAATGTTACA NC_045512.2_21mer_win1_29692 29692 29712 3329CATTGTAATCCCTCCTGAACT 4311 TCAAGTCCTCCCTAATGTTACNC_045512.2_21mer_win1_29693 29693 29713 3330 ATTGTAATCCCTCCTGAACTT 4312TTCAAGTCCTCCCTAATGTTA NC_045512.2_21mer_win1_29694 29694 29714 3331TTGTAATCCCTCCTGAACTTT 4313 TTTCAAGTCCTCCCTAATGTTNC_045512.2_21mer_win1_29695 29695 29715 3332 TGTAATCCCTCCTGAACTTTC 4314CTTTCAAGTCCTCCCTAATGT NC_045512.2_21mer_win1_29696 29696 29716 3333GTAATCCCTCCTGAACTTTCT 4315 TCTTTCAAGTCCTCCCTAATGNC_045512.2_21mer_win1_29697 29697 29717 3334 TAATCCCTCCTGAACTTTCTC 4316CTCTTTCAAGTCCTCCCTAAT NC_045512.2_21mer_win1_29698 29698 29718 3335AATCCCTCCTGAACTTTCTCG 4317 GCTCTTTCAAGTCCTCCCTAANC_045512.2_21mer_win1_29699 29699 29719 3336 ATCCCTCCTGAACTTTCTCGG 4318GGCTCTTTCAAGTCCTCCCTA NC_045512.2_21mer_win1_29700 29700 29720 3337TCCCTCCTGAACTTTCTCGGT 4319 TGGCTCTTTCAAGTCCTCCCTNC_045512.2_21mer_win1_29701 29701 29721 3338 CCCTCCTGAACTTTCTCGGTG 4320GTGGCTCTTTCAAGTCCTCCC NC_045512.2_21mer_win1_29702 29702 29722 3339CCTCCTGAACTTTCTCGGTGG 4321 GGTGGCTCTTTCAAGTCCTCCNC_045512.2_21mer_win1_29703 29703 29723 3340 CTCCTGAACTTTCTCGGTGGT 4322TGGTGGCTCTTTCAAGTCCTC NC_045512.2_21mer_win1_29704 29704 29724 3341TCCTGAACTTTCTCGGTGGTG 4323 GTGGTGGCTCTTTCAAGTCCTNC_045512.2_21mer_win1_29705 29705 29725 3342 CCTGAACTTTCTCGGTGGTGT 4324TGTGGTGGCTCTTTCAAGTCC NC_045512.2_21mer_win1_29706 29706 29726 3343CTGAACTTTCTCGGTGGTGTA 4325 ATGTGGTGGCTCTTTCAAGTCNC_045512.2_21mer_win1_29707 29707 29727 3344 TGAACTTTCTCGGTGGTGTAA 4326AATGTGGTGGCTCTTTCAAGT NC_045512.2_21mer_win1_29708 29708 29728 3345GAACTTTCTCGGTGGTGTAAA 4327 AAATGTGGTGGCTCTTTCAAGNC_045512.2_21mer_win1_29709 29709 29729 3346 AACTTTCTCGGTGGTGTAAAA 4328AAAATGTGGTGGCTCTTTCAA NC_045512.2_21mer_win1_29710 29710 29730 3347ACTTTCTCGGTGGTGTAAAAG 4329 GAAAATGTGGTGGCTCTTTCANC_045512.2_21mer_win1_29711 29711 29731 3348 CTTTCTCGGTGGTGTAAAAGT 4330TGAAAATGTGGTGGCTCTTTC NC_045512.2_21mer_win1_29733 29733 29753 3349GCTCCGGTGCGCCTCATGCTA 4331 ATCGTACTCCGCGTGGCCTCGNC_045512.2_21mer_win1_29734 29734 29754 3350 CTCCGGTGCGCCTCATGCTAG 4332GATCGTACTCCGCGTGGCCTC NC_045512.2_21mer_win1_29735 29735 29755 3351TCCGGTGCGCCTCATGCTAGC 4333 CGATCGTACTCCGCGTGGCCTNC_045512.2_21mer_win1_29736 29736 29756 3352 CCGGTGCGCCTCATGCTAGCT 4334TCGATCGTACTCCGCGTGGCC NC_045512.2_21mer_win1_29737 29737 29757 3353CGGTGCGCCTCATGCTAGCTC 4335 CTCGATCGTACTCCGCGTGGCNC_045512.2_21mer_win1_29770 29770 29790 3354 TTACGATCCCTCTCGACGGAT 4336TAGGCAGCTCTCCCTAGCATT NC_045512.2_21mer_win1_29771 29771 29791 3355TACGATCCCTCTCGACGGATA 4337 ATAGGCAGCTCTCCCTAGCATNC_045512.2_21mer_win1_29772 29772 29792 3356 ACGATCCCTCTCGACGGATAT 4338TATAGGCAGCTCTCCCTAGCA NC_045512.2_21mer_win1_29773 29773 29793 3357CGATCCCTCTCGACGGATATA 4339 ATATAGGCAGCTCTCCCTAGCNC_045512.2_21mer_win1_29774 29774 29794 3358 GATCCCTCTCGACGGATATAC 4340CATATAGGCAGCTCTCCCTAG NC_045512.2_21mer_win1_29775 29775 29795 3359ATCCCTCTCGACGGATATACC 4341 CCATATAGGCAGCTCTCCCTANC_045512.2_21mer_win1_29776 29776 29796 3360 TCCCTCTCGACGGATATACCT 4342TCCATATAGGCAGCTCTCCCT NC_045512.2_21mer_win1_29777 29777 29797 3361CCCTCTCGACGGATATACCTT 4343 TTCCATATAGGCAGCTCTCCCNC_045512.2_21mer_win1_29778 29778 29798 3362 CCTCTCGACGGATATACCTTC 4344CTTCCATATAGGCAGCTCTCC NC_045512.2_21mer_win1_29779 29779 29799 3363CTCTCGACGGATATACCTTCT 4345 TCTTCCATATAGGCAGCTCTCNC_045512.2_21mer_win1_29780 29780 29800 3364 TCTCGACGGATATACCTTCTC 4346CTCTTCCATATAGGCAGCTCT NC_045512.2_2lmer_win1_29781 29781 29801 3365CTCGACGGATATACCTTCTCG 4347 GCTCTTCCATATAGGCAGCTCNC_045512.2_21mer_win1_29782 29782 29802 3366 TCGACGGATATACCTTCTCGG 4348GGCTCTTCCATATAGGCAGCT NC_045512.2_21mer_win1_29783 29783 29803 3367CGACGGATATACCTTCTCGGG 4349 GGGCTCTTCCATATAGGCAGCNC_045512.2_21mer_win1_29784 29784 29804 3368 GACGGATATACCTTCTCGGGA 4350AGGGCTCTTCCATATAGGCAG NC_045512.2_21mer_win1_29785 29785 29805 3369ACGGATATACCTTCTCGGGAT 4351 TAGGGCTCTTCCATATAGGCANC_045512.2_21mer_win1_29786 29786 29806 3370 CGGATATACCTTCTCGGGATT 4352TTAGGGCTCTTCCATATAGGC NC_045512.2_21mer_win1_29787 29787 29807 3371GGATATACCTTCTCGGGATTA 4353 ATTAGGGCTCTTCCATATAGGNC_045512.2_21mer_win1_29788 29788 29808 3372 GATATACCTTCTCGGGATTAC 4354CATTAGGGCTCTTCCATATAG NC_045512.2_21mer_win1_29789 29789 29809 3373ATATACCTTCTCGGGATTACA 4355 ACATTAGGGCTCTTCCATATANC_045512.2_21mer_win1_29790 29790 29810 3374 TATACCTTCTCGGGATTACAC 4356CACATTAGGGCTCTTCCATAT NC_045512.2_2lmer_win1_29791 29791 29811 3375ATACCTTCTCGGGATTACACA 4357 ACACATTAGGGCTCTTCCATANC_045512.2_21mer_win1_29792 29792 29812 3376 TACCTTCTCGGGATTACACAT 4358TACACATTAGGGCTCTTCCAT NC_045512.2_21mer_win1_29793 29793 29813 3377ACCTTCTCGGGATTACACATT 4359 TTACACATTAGGGCTCTTCCANC_045512.2_21mer_win1_29794 29794 29814 3378 CCTTCTCGGGATTACACATTT 4360TTTACACATTAGGGCTCTTCC NC_045512.2_21mer_win1_29795 29795 29815 3379CTTCTCGGGATTACACATTTT 4361 TTTTACACATTAGGGCTCTTCNC_045512.2_21mer_win1_29796 29796 29816 3380 TTCTCGGGATTACACATTTTA 4362ATTTTACACATTAGGGCTCTT NC_045512.2_21mer_win1_29797 29797 29817 3381TCTCGGGATTACACATTTTAA 4363 AATTTTACACATTAGGGCTCTNC_045512.2_21mer_win1_29798 29798 29818 3382 CTCGGGATTACACATTTTAAT 4364TAATTTTACACATTAGGGCTC NC_045512.2_21mer_win1_29799 29799 29819 3383TCGGGATTACACATTTTAATT 4365 TTAATTTTACACATTAGGGCTNC_045512.2_21mer_win1_29800 29800 29820 3384 CGGGATTACACATTTTAATTA 4366ATTAATTTTACACATTAGGGC NC_045512.2_21mer_win1_29801 29801 29821 3385GGGATTACACATTTTAATTAA 4367 AATTAATTTTACACATTAGGGNC_045512.2_21mer_win1_29802 29802 29822 3386 GGATTACACATTTTAATTAAA 4368AAATTAATTTTACACATTAGG NC_045512.2_21mer_win1_29803 29803 29823 3387GATTACACATTTTAATTAAAA 4369 AAAATTAATTTTACACATTAGNC_045512.2_21mer_win1_29804 29804 29824 3388 ATTACACATTTTAATTAAAAT 4370TAAAATTAATTTTACACATTA NC_045512.2_21mer_win1_29805 29805 29825 3389TTACACATTTTAATTAAAATC 4371 CTAAAATTAATTTTACACATTNC_045512.2_21mer_win1_29806 29806 29826 3390 TACACATTTTAATTAAAATCA 4372ACTAAAATTAATTTTACACAT NC_045512.2_21mer_win1_29807 29807 29827 3391ACACATTTTAATTAAAATCAT 4373 TACTAAAATTAATTTTACACANC_045512.2_21mer_win1_29808 29808 29828 3392 CACATTTTAATTAAAATCATC 4374CTACTAAAATTAATTTTACAC

TABLE 2 Genome Sequences for Coronaviruses SEQ ID Des- NO criptionSequence 2407 SARS-CoV-attaaaggtttataccttcccaggtaacaaaccaaccaactttcgatctcttgtagatctgttctctaaacgaactttaaaatctgtgtggctgtcactcggctgcatgcttagtgc2 genomeactcacgcagtataattaataactaattactgtcgttgacaggacacgagtaactcgtctatcttctgcaggctgcttacggtttcgtccgtgttgcagccgatcatcagcacat(GenbankctaggtttcgtccgggtgtgaccgaaaggtaagatggagagccttgtccctggtttcaacgagaaaacacacgtccaactcagtttgcctgttttacaggttcgcgacgtgctAccessioncgtacgtggctttggagactccgtggaggaggtatatcagaggcacgtcaacatcttaaagatggcacttgtggcttagtagaagttgaaaaaggcgttttgcctcaacttgNo.aacagccctatgtgttcatcaaacgttcggatgctcgaactgcacctcatggtcatgttatggttgagctggtagcagaactcgaaggcattcagtacggtcgtagtggtgagNC_acacttggtgtccttgtccctcatgtgggcgaaataccagtggcttaccgcaaggttcttcttcgtaagaacggtaataaaggagctggtggccatagttacggcgccgatct045512.2)aaagtcatttgacttaggcgacgagcttggcactgatccttatgaagattttcaagaaaactggaacactaaacatagcagtggtgttacccgtgaactcatgcgtgagcttaacggaggggcatacactcgctatgtcgataacaacttctgtggccctgatggctaccctcttgagtgcattaaagaccttctagcacgtgctggtaaagcttcatgcactttgtccgaacaactggactttattgacactaagaggggtgtatactgctgccgtgaacatgagcatgaaattgcttggtacacggaacgttctgaaaagagctatgaattgcagacacatttgaaattaaattggcaaagaaatttgacaccttcaatggggaatgtccaaattttgtatttcccttaaattccataatcaagactattcaaccaagggttgaaaagaaaaagcttgatggctttatgggtagaattcgatctgtctatccagttgcgtcaccaaatgaatgcaaccaaatgtgcctttcaactctcatgaagtgtgatcattgtggtgaaacttcatggcagacgggcgattttgttaaagccacttgcgaattttgtggcactgagaatttgactaaagaaggtgccactacttgtggttacttaccccaaaatgctgttgttaaaatttattgtccagcatgtcacaattcagaagtaggacctgagcatagtcttgccgaataccataatgaatctggcttgaaaaccattcttcgtaagggtggtcgcactattgcctttggaggctgtgtgttctcttatgttggttgccataacaagtgtgcctattgggttccacgtgctagcgctaacataggttgtaaccatacaggtgttgttggagaaggttccgaaggtcttaatgacaaccttcttgaaatactccaaaaagagaaagtcaacatcaatattgttggtgactttaaacttaatgaagagatcgccattattttggcatctttttctgcttccacaagtgatttgtggaaactgtgaaaggtttggattataaagcattcaaacaaattgttgaatcctgtggtaattttaaagttacaaaaggaaaagctaaaaaaggtgcctggaatattggtgaacagaaatcaatactgagtcctattatgcatttgcatcagaggctgctcgtgttgtacgatcaattttctcccgcactcttgaaactgctcaaaattctgtgcgtgttttacagaaggccgctataacaatactagatggaatttcacagtattcactgagactcattgatgctatgatgttcacatctgatttggctactaacaatctagttgtaatggcctacattacaggtggtgttgttcagttgacttcgcagtggctaactaacatattggcactgtttatgaaaaactcaaacccgtccttgattggcttgaagagaagtttaaggaaggtgtagagtttcttagagacggttgggaaattgttaaatttatctcaacctgtgcttgtgaaattgtcggtggacaaattgtcacctgtgcaaaggaaattaaggagagtgttcagacattctttaagcttgtaaataaatttttggctttgtgtgctgactctatcattattggtggagctaaacttaaagccttgaatttaggtgaaacatttgtcacgcactcaaagggattgtacagaaagtgtgttaaatccagagaagaaactggcctactcatgcctctaaaagccccaaaagaaattatcttcttagagggagaaacacttcccacagaagtgttaacagaggaagttgtcttgaaaactggtgatttacaaccattagaacaacctactagtgaagctgttgaagctccattggttggtacaccagtttgtattaacgggcttatgttgctcgaaatcaaagacacagaaaagtactgtgccatgcacctaatatgatggtaacaaacaataccttcacactcaaaggcggtgcaccaacaaaggttacttttggtgatgacactgtgatagaagtgcaaggttacaagagtgtgaatatcacttttgaacttgatgaaaggattgataaagtacttaatgagaagtgctctgcctatacagttgaactcggtacagaagtaaatgagttcgcctgtgttgtggcagatgctgtcataaaaactttgcaaccagtatctgaattacttacaccactgggcattgatttagatgagtggagtatggctacatactacttatttgatgagtaggtgagtttaaattggcttcacatatgtattgttattctaccctccagatgaggatgaagaagaaggtgattgtgaagaagaagagtttgagccatcaactcaatatgagtatggtactgaagatgattaccaaggtaaacctttggaatttggtgccacttctgctgacttcaacctgaagaagagcaagaagaagattggttagatgatgatagtcaacaaactgttggtcaacaagacggcagtgaggacaatcagacaactactattcaaacaattgttgaggttcaacctcaattagagatggaacttacaccagttgttcagactattgaagtgaatagttttagtggttatttaaaacttactgacaatgtatacattaaaaatgcagacattgtggaagaagctaaaaaggtaaaaccaacagtggttgttaatgcagccaatgtttaccttaaacatggaggaggtgttgcaggagccttaaataaggctactaacaatgccatgcaagttgaatctgatgattacatagctactaatggaccacttaaagtgggtggtagttgtgttttaagcggacacaatcttgctaaacactgtcttcatgttgtcggcccaaatgttaacaaaggtgaagacattcaacttcttaagagtgcttatgaaaattttaatcagcacgaagttctacttgcaccattattatcagaggtatttttggtgctgaccctatacattattaagagtttgtgtagatactgttcgcacaaatgtctacttagctgtctttgataaaaatctctatgacaaacttgtttcaagattttggaaatgaagagtgaaaagcaagttgaacaaaagatcgctgagattcctaaagaggaagttaagccatttataactgaaagtaaaccttcagttgaacagagaaaacaagatgataagaaaatcaaagcttgtgttgaagaagttacaacaactctggaagaaactaagttcctcacagaaaacttgttactttatattgacattaatggcaatcttcatccagattctgccactcttgttagtgacattgacatcactttcttaaagaaagatgctccatatatagtgggtgatgttgttcaagagggtgttttaactgctgtggttatacctactaaaaaggctggtggcactactgaaatgctagcgaaagctttgagaaaagtgccaacagacaattatataaccacttacccgggtcagggtttaaatggttacactgtagaggaggcaaagacagtgcttaaaaagtgtaaaagtgccttttacattctaccatctattatctctaatgagaagcaagaaattcttggaactgtttcttggaatttgcgagaaatgcttgcacatgcagaagaaacacgcaaattaatgcctgtagtgtggaaactaaagccatagtttcaactatacagcgtaaatataagggtattaaaatacaagagggtgtggttgattatggtgctagattttacttttacaccagtaaaacaactgtagcgtcacttatcaacacacttaacgatctaaatgaaactcttgttacaatgccacttggctatgtaacacatggcttaaatttggaagaagctgctcggtatatgagatctctcaaagtgccagctacagtttctgtttcttcacctgatgctgttacagcgtataatggttatcttacttcttcttctaaaacacctgaagaacattttattgaaaccatctcacttgctggttcctataaagattggtcctattctggacaatctacacaactaggtatagaatttcttaagagaggtgataaaagtgtatattacactagtaatcctaccacattccacctagatggtgaagttatcacctttgacaatcttaagacacttattctttgagagaagtgaggac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2408 SARS-CoV-atattaggtttttacctacccaggaaaagccaaccaacctcgatctcttgtagatctgttctctaaacgaactttaaaatctgtgtagctgtcgctcggctgcatgcctagtgcac1 genomectacgcagtataaacaataataaattttactgtcgttgacaagaaacgagtaactcgtccctcttctgcagactgcttacggtttcgtccgtgttgcagtcgatcatcagcatacc(GenbanktaggtttcgtccgggtgtgaccgaaaggtaagatggagagccttgttcttggtgtcaacgagaaaacacacgtccaactcagtttgcctgtccttcaggttagagacgtgctaAccessiongtgcgtggcttcggggactctgtggaagaggccctatcggaggcacgtgaacacctcaaaaatggcacttgtggtctagtagagctggaaaaaggcgtactgccccagcNo.ttgaacagccctatgtgttcattaaacgttctgatgccttaagcaccaatcacggccacaaggtcgttgagctggttgcagaaatggacggcattcagtacggtcgtagcggtNC_ataacactgggagtactcgtgccacatgtgggcgaaaccccaattgcataccgcaatgttcttcttcgtaagaacggtaataagggagccggtggtcatagctatggcatc004718.3)gatctaaagtcttatgacttaggtgacgagcttggcactgatcccattgaagattatgaacaaaactggaacactaagcatggcagtggtgcactccgtgaactcactcgtgagctcaatggaggtgcagtcactcgctatgtcgacaacaatttctgtggcccagatgggtaccctcttgattgcatcaaagattttctcgcacgcgcgggcaagtcaatgtgcactctttccgaacaacttgattacatcgagtcgaagagaggtgtctactgctgccgtgaccatgagcatgaaattgcctggttcactgagcgctctgataagagctacgagcaccagacacccttcgaaattaagagtgccaagaaatttgacactttcaaaggggaatgcccaaagtttgtgtttcctcttaactcaaaagtcaaagtcattcaaccacgtgttgaaaagaaaaagactgagggtttcatggggcgtatacgctctgtgtaccctgttgcatctccacaggagtgtaacaatatgcacttgtctaccttgatgaaatgtaatcattgcgatgaagtttcatggcagacgtgcgactttctgaaagccacttgtgaacattgtggcactgaaaatttagttattgaaggacctactacatgtgggtacctacctactaatgctgtagtgaaaatgccatgtcctgcctgtcaagacccagagattggacctgagcatagtgttgcagattatcacaaccactcaaacattgaaactcgactccgcaagggaggtaggactagatgttttggaggctgtgtgtttgcctatgttggctgctataataagcgtgcctactgggttcctcgtgctagtgctgatattggctcaggccatactggcattactggtgacaatgtggagaccttgaatgaggatctccttgagatactgagtcgtgaacgtgttaacattaacattgttggcgattttcatttgaatgaagaggttgccatcattttggcatctttctctgcttctacaagtgcctttattgacactataaagagtcttgattacaagtattcaaaaccattgttgagtcctgcggtaactataaagttaccaagggaaagcccgtaaaaggtgcttggaacattggacaacagagatcagttttaacaccactgtgtggttttccctcacaggctgctggtgttatcagatcaatttttgcgcgcacacttgatgcagcaaaccactcaattcctgatttgcaaagagcagctgtcaccatacttgatggtatttctgaacagtcattacgtcttgtcgacgccatggtttatacttcagacctgctcaccaacagtgtcattattatggcatatgtaactggtggtcttgtacaacagacttctcagtggttgtctaatcttttgggcactactgttgaaaaactcaggcctatctttgaatggattgaggcgaaacttagtgcaggagttgaatttctcaaggatgcttgggagattctcaaatttctcattacaggtgtttttgacatcgtcaagggtcaaatacaggttgcttcagataacatcaaggattgtgtaaaatgcttcattgatgttgttaacaaggcactcgaaatgtgcattgatcaagtcactatcgctggcgcaaagttgcgatcactcaacttaggtgaagtcttcatcgctcaaagcaagggactttaccgtcagtgtatacgtggcaaggagcagctgcaactactcatgcctcttaaggcaccaaaagaagtaacctttcttgaaggtgattcacatgacacagtacttacctctgaggaggttgttctcaagaacggtgaactcgaagcactcgagacgcccgttgatagcttcacaaatggagctatcgttggcacaccagtagtgtaaatggcctcatgacttagagattaaggacaaagaacaatactgcgcattgtctcctggtttactggctacaaacaatgtattcgcttaaaagggggtgcaccaattaaaggtgtaacattggagaagatactgtttgggaagttcaaggttacaagaatgtgagaatcacatttgagcttgatgaacgtgttgacaaagtgcttaatgaaaagtgactgtctacactgttgaatccggtaccgaagttactgagtttgcatgtgttgtagcagaggctgttgtgaagactttacaaccagtttctgatctccttaccaacatgggtattgatcttgatgagtggagtgtagctacattctacttatttgatgatgctggtgaagaaaacttttcatcacgtatgtattgttccttttaccctccagatgaggaagaagaggacgatgcagagtgtgaggaagaagaaattgatgaaacctgtgaacatgagtacggtacagaggatgattatcaaggtaccactggaatttggtgcctcagctgaaacagttcgagttgaggaagaagaagaggaagactggctggatgatactactgagcaatcagagattgagccagaaccagaacctacacctgaagaaccagttaatcagtttactggttatttaaaacttactgacaatgttgccattaaatgtgttgacatcgttaaggaggcacaaagtgctaatcctatggtgattgtaaatgctgctaacatacacctgaaacatggtggtggtgtagcaggtgcactcaacaaggcaaccaatggtgccatgcaaaaggagagtgatgattacattaagctaaatggccctcttacagtaggagggtcttgtttgattctggacataatcttgctaagaagtgtctgcatgttgttggacctaacctaaatgcaggtgaggacatccagcttcttaaggcagcatatgaaaatttcaattcacaggacatcttacttgcaccattgttgtcagcaggcatatttggtgctaaaccacttcagtattacaagtgtgcgtgcagacggttcgtacacaggtttatattgcagtcaatgacaaagctctttatgagcaggttgtcatggattatcttgataacctgaagcctagagtggaagcacctaaacaagaggagccaccaaacacagaagattccaaaactgaggagaaatctgtcgtacagaagcctgtcgatgtgaagccaaaaattaaggcctgcattgatgaggttaccacaacactggaagaaactaagtttcttaccaataagttactcttgtttgctgatatcaatggtaagattaccatgattctcagaacatgcttagaggtgaagatatgtctttccttgagaaggatgcaccttacatggtaggtgatgttatcactagtggtgatatcacttgtgttgtaataccctccaaaaaggctggtggcactactgagatgctctcaagagctttgaagaaagtgccagttgatgagtatataaccacgtaccctggacaaggatgtgctggttatacacttgaggaagctaagactgctcttaagaaatgcaaatctgcattttatgtactaccttcagaagcacctaatgctaaggaagagattctaggaactgtatcctggaatttgagagaaatgcttgctcatgctgaagagacaagaaaattaatgcctatatgcatggatgttagagccataatggcaaccatccaacgtaagtataaaggaattaaaattcaagagggcatcgttgactatggtgtccgattcttcttttatactagtaaagagcctgtagcttctattattacgaagctgaactctctaaatgagccgcttgtcacaatgccaattggttatgtgacacatggttttaatcttgaagaggctgcgcgctgtatgcgttctcttaaagctcctgccgtagtgtcagtatcatcaccagatgctgttactacatataatggatacctcacttcgtcatcaaagacatctgaggagcactttgtagaaacagtttattggctggctcttacagagattggtcctattcaggacagcgtacagagttaggtgttgaatttcttaagcgtggtgacaaaattgtgtaccacactctggagagccccgtcgagtttcatcttgacggtgaggttctttcacttgacaaactaaagagtctcttatccctgcgggaggttaagactataaaagtgttcacaactgtggacaacactaatctccacacacagcttgtggatatgtctatgacat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2409 MERS-CoVgatttaagtgaatagcttggctatctcacttcccctcgttctcttgcagaactttgattttaacgaacttaaataaaagccctgttgtttagcgtatcgttgcacttgtctggtgggatgenometgtggcattaatttgcctgctcatctaggcagtggacatatgctcaacactgggtataattctaattgaatactatttttcagttagagcgtcgtgtctcttgtacgtctcggtcaca(GenbankatacacggtttcgtccggtgcgtggcaattcggggcacatcatgtctttcgtggctggtgtgaccgcgcaaggtgcgcgcggtacgtatcgagcagcgctcaactctgaaaAccessionaacatcaagaccatgtgtctctaactgtgccactctgtggttcaggaaacctggttgaaaaactttcaccatggttcatggatggcgaaaatgcctatgaagtggtgaaggccNo.atgttacttaaaaaggagccacttctctatgtgcccatccggctggctggacacactagacacctcccaggtcctcgtgtgtacctggttgagaggctcattgcttgtgaaaatNC_ccattcatggttaaccaattggcttatagctctagtgcaaatggcagcctggttggcacaactttgcagggcaagcctattggtatgttcttcccttatgacatcgaacttgtcac019843.3)aggaaagcaaaatattctcctgcgcaagtatggccgtggtggttatcactacaccccattccactatgagcgagacaacacctcttgccctgagtggatggacgattttgaggcggatcctaaaggcaaatatgcccagaatctgcttaagaagttgattggcggtgatgtcactccagttgaccaatacatgtgtggcgttgatggaaaacccattagtgcctacgcatttttaatggccaaggatggaataaccaaactggctgatgttgaagcggacgtcgcagcacgtgctgatgacgaaggcttcatcacattaaagaacaatctatatagattggtttggcatgttgagcgtaaagacgttccatatcctaagcaatctatttttactattaatagtgtggtccaaaaggatggtgttgaaaacactcctcctcactattttactcttggatgcaaaattttaacgctcaccccacgcaacaagtggagtggcgtttctgacttgtccctcaaacaaaaactcctttacaccttctatggtaaggagtcacttgagaacccaacctacatttaccactccgcattcattgagtgtggaagttgtggtaatgattcctggcttacagggaatgctatccaagggtttgcctgtggatgtggggcatcatatacagctaatgatgtcgaagtccaatcatctggcatgattaagccaaatgctcttctttgtgctacttgcccctttgctaagggtgatagctgttcttctaattgcaaacattcagttgctcagttggttagttacctttctgaacgctgtaatgttattgctgattctaagtccttcacacttatattggtggcgtagcttacgcctactttggatgtgaggaaggtactatgtactttgtgcctagagctaagtctgttgtctcaaggattggagactccatctttacaggctgtactggctcttggaacaaggtcactcaaattgctaacatgttcttggaacagactcagcattcccttaactttgtgggagagttcgttgtcaacgatgttgtcctcgcaattctctctggaaccacaactaatgttgacaaaatacgccagcttctcaaaggtgtcacccttgacaagttgcgtgattatttagctgactatgacgtagcagtcactgccggcccattcatggataatgctattaatgttggtggtacaggattacagtatgccgccattactgcaccttatgtagttctcactggcttaggtgagtcctttaagaaagttgcaaccataccgtataaggtttgcaactctgttaaggatactctggcttattatgctcacagcgtgttgtacagagtttttccttatgacatggattctggtgtgtcatcctttagtgaactactttttgattgcgttgatattcagtagcttctacctattttttagtccgcatcttgcaagataagactggcgactttatgtctacaattattacttcctgccaaactgctgttagtaagcttctagatacatgttttgaagctacagaagcaacatttaacttcttgttagatttggcaggattgttcagaatctttctccgcaatgcctatgtgtacacttcacaagggtttgtggtggtcaatggcaaagtttctacacttgtcaaacaagtgttagacttgcttaataagggtatgcaacttttgcatacaaaggtctcctgggctggttctaaaatcattgctgttatctacagcggcagggagtctctaatattcccatcgggaacctattactgtgtcaccactaaggctaagtccgttcaacaagatcttgacgttatt-ttgcctggtgagttttccaagaagcagttaggactgctccaacctactgacaattctacaactgttagtgttactgtatccagtaacatggttgaaactgttgtgggtcaacttgagcaaactaatatgcatagtcctgatgttatagtaggtgactatgtcattattagtgaaaaattgtttgtgcgtagtaaggaagaagacggatttgccttctaccctgcttgcactaatggtcatgctgtaccgactctctttagacttaagggaggtgcacctgtaaaaaaagtagcctttggcggtgatcaagtacatgaggttgctgctgtaagaagtgttactgtcgagtacaacattcatgctgtattagacacactacttgcttcttctagtcttagaacctttgttgtagataagtctttgtcaattgaggagtttgctgacgtagtaaaggaacaagtctcagacttgcttgttaaattactgcgtggaatgccgattccagattttgatttagacgattttattgacgcaccatgctattgctttaacgctgagggtgatgcatcctggtcttctactatgatcttctctcttcaccccgtcgagtgtgacgaggagtgttctgaagtagaggcttcagatttagaagaaggtgaatcagagtgcatttctgagacttcaactgaacaagttgacgtttctcatgagacttctgacgacgagtgggctgctgcagttgatgaagcgttccctctcgatgaagcagaagatgttactgaatctgtgcaagaagaagcacaaccagtagaagtacctgttgaagatattgcgcaggttgtcatagctgacaccttacaggaaactcctgttgtgcctgatactgttgaagtcccaccgcaagtggtgaaacttccgtctgcacctcagactatccagcccgaggtaaaagaagttgcacctgtctatgaggctgataccgaacagacacagaatgttactgttaaacctaagaggttacgcaaaaagcgtaatgttgaccattgtccaattttgaacataaggttattacagagtgcgttaccatagttttaggtgacgcaattcaagtagccaagtgctatggggagtctgtgttagttaatgctgctaacacacatcttaagcatggcggtggtatcgctggtgctattaatgcggcttcaaaaggggctgtccaaaaagagtcagatgagtatattctggctaaagggccgttacaagtaggagattcagttctcttgcaaggccattctctagctaagaatatcctgcatgtcgtaggcccagatgcccgcgctaaacaggatgtttctctccttagtaagtgctataaggctatgaatgcatatcctcttgtagtcactcctcttgtttcagcaggcatatttggtgtaaaaccagctgtgtcttttgattatcttattagggaggctaagactagagttttagtcgtcgttaattcccaagatgtctataagagtcttaccatagttgacattccacagagtttgactttttcatatgatgggttacgtggcgcaatacgtaaagctaaagattatggttttactgtttttgtgtgcacagacaactctgctaacactaaagttcttaggaacaagggtgttgattatactaagaagtttcttacagttgacggtgtgcaatattattgctacacgtctaaggacactttagatgatatcttacaacaggctaataagtagttggtattatatctatgcctttgggatatgtgtctcatggtttagacttaatgcaagcagggagtgtcgtgcgtagagttaacgtgccctacgtgtgtctcctagctaataaagagcaagaagctattttgatgtctgaagacgttaagttaaacccttcagaagattttataaagcacgtccgcactaatggtggttacaattcttggcatttagtcgagggtgaactattggtgcaagacttacgcttaaataagctcctgcattggtctgatcaaaccatatgctacaaggatagtgtgttttatgttgtaaagaatagtacagcttttccatttgaaacactttcagcatgtcgtgcgtatttggattcacgcacgacacagcagttaacaatcgaagtcttagtgactgtcgatggtgtaaattttagaacagtcgttctaaataataagaacacttatagatcacagcttggatgcgttttattaatggtgctgatatttctgacaccattcctgatgagaaacagaatggtcacagtttatatctagcagacaatttgactgctgatgaaacaaaggcgcttaaagagttatatggccccgttgatcctactttc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acagtgccccccgggaagagctctacagtgtgaaatgtaaataaaaaatagctattattcaattagattaggctaattagatgatttgcaaaaaaaaaaaa 2410 hCoV-attgtgagcgatttgcgtgcgtgcatcccgcttcactgatctcttgttagatattttgtaatctaaactttataaaaacatccactccctgtaatctatgcttgtgggcgtagatttttOC43catagtggtgtttatattcatttctgctgttaacagattcagccagggacgtgttgtatcctaggcagtggcccgcccataggtcacaatgtcgaagatcaacaaatacggtctgenomecgaactacactgggctccagaatttccatggatgtttgaggacgcagaggagaagttggataaccctagtagttcagaggtggatatgatttgctccaccactgcgcaaaa(GenbankgctggaaacagacggaatttgtcctgaaaatcatgtgatggtggattgtcgccgacttcttaaacaagagtgttgtgtgcagtctagcctaatacgtgaaattgttatgaatgcAccessionaagtccatatgatttggaggtgctacttcaagatgattgcagtcccgtgaagcagttttggttacaacccccttaggtatgtctttagaggcatgctatgtgagaggttgtaatcNo.ctaaaggatggaccatgggtttgtttcggcgtagaagtgtgtgtaacactggtcgttgcactgttaataagcatgtggcctatcagttatatatgattgatcctgcaggtgtctgtNC_cttggtgcaggtcaattcgtgggttgggtcatacccttagcctttatgcctgtgcaatcccggaaatttattgttccatgggttatgtacttgcgtaagcgtggcgaaaagggtg006213.1)cttacaataaagatcatggacgtggcggttttggacatgtttatgattttaaagttgaagatgcttatgaccaggtgcatgatgagcctaagggtaagttttctaagaaggcttatgctttaattagagggtatcgtggtgttaaaccacttctctatgtagaccagtatggttgtgattatactggtagtcttgcagatggcttagaggcttatgctgataagacattgcaagaaatgaaggcattatttcctacttggagtcaggaactcctttttgatgtaattgtggcatggcatgttgtgcgtgatccacgttatgttatgagattgcagagtgctgctactatacgtagtgttgcatatgttgctaatcctactgaagacttgtgtgatggttctgttgttataaaagaacctgtgcatgtttatgcagatgactctattattttacgtcaatataatttagttgacattatgagtcatttttatatggaggcagatacagttgtaaatgctttttatggtgttgctttgaaagattgcggttttgttatgcagtttggttacattgattgcgaacaagactcgtgtgattttaaaggttggattcctggtaacatgatagatggttttgcttgcaccacttgtggtcatgtttatgaagtaggtgatttgatggcacaatcttcaggtgttttgcctgttaaccctgtattgcatactaagagtgcagcaggctatggtggttttggttgtaaagattcttttactctgtatggccaaactgtagtttattttggaggttgtgtgtattggagtccagcacgtaatatatggattcctatattaaaatcctagttaagtcatatgacagtttggtttatactggagttttaggttgcaaggctattgtaaaggaaacaaatctcatttgcaaagctttgtaccttgattatgttcaacacaagtgtggcaatttacaccaacgggagttgctaggtgtttcagatgtgtggcataaacaattgctattaaatagaggtgtttataaacctctgttagagaatattgattattttaatatgcggcgcgctaaatttagtttagaaacttttactgtttgtgcagatggctttatgccttttcttttagatgatttagttccacgcgcatattatttggcagtaagtggtcaagcattttgtgattatgcagataaactttgccatgccgttgtgtctaagagtaaagagttacttgatgtgtctctggattattaggtgcagctatacattatttgaattctaagattgttgatttggctcaacattttagtgattttggaacaagtttcgtttctaaaattgttcatttattaagacttttactactagcactgctcttgcatttgcatgggttttatttcatgttttgcatggtgcttatatagtagtggagagtgatatatattttgttaaaaacattcctcgttatgctagtgctgttgcacaagcatttcagagtgttgctaaagttgtactggactctttaagagttacttttattgatggcctttcttgttttaagattggacgtagaagaatttgtctttcaggcagaaaaatttatgaagttgagcgtggcttgttacattcatcccaattgccattagatgtttatgatttaaccatgcctagtcaagttcagaaagccaagcaaaaacctatttatttaaaaggttctggttctgatttttcattagcggatagtgtagttgaagttgttacaacttcacttacaccatgtggttattctgaaccacctaaagttgcagctaaaatttgcattgtggataatgtttatatggccaaggctggtgacaaatattaccctgttgtggttgatgatcatgttggactcttggatcaagcatggagagttccttgtgctggaaggcgtgttacatttaaggaacagcctacagtaaaggagattataagcatgcctaagattattaaggttttttatgagcttgacaacgattttaatactattttaaatactgcgtgtggagtgtttgaagtggatgatactgttgatatggaggaattttatgctgtggtgattgatgccatagaagagaaactttaccatgtaaggagcttgaaggtgtaggtgctaaagttagtgcctttttacagaaattagaggataatcccctatttttatttgatgaggctggcgaggaagttcttgctcctaaattgtattgtgcctttacagctcctgaagatgatgactttcttgaggaaagtgatgttgaagaagatgatgtagaaggtgaggaaactgatttaactgtcacaagtgctggacagccttgtgttgctagtgaacaggaggagtcttctgaagtcttagaggacactttggatgatggtccaagtgtggagacatctgattcacaagttgaagaagatgtagaaatgtcggattttgttgatcttgaatctgtgattcaggattatgaaaatgtttgttttgagttttatactacagagccagaatttgttaaagttttgggtctgtatgtgcctaaagcaactcgcaacaattgctggttgcgatcagttttggcagtgatgcagaaattgccctgtcaatttaaagataaaaatttgcaggatctttgggtgttatacaagcaacagtatagtcagttgtttgttgataccttggttaataagatacctgctaatattgtacttccacaaggtggttatgttgctgattttgcatattggtttttaaccttatgtgattggcagtgtgttgcatactggaaatgcattaaatgtgatttagctcttaagcttaaaggcttggatgctatgttcttttatggtgatgttgtttcacatatatgcaagtgtggtgagtctatggtacttattgatgttgatgtgccatttacagcccactttgctcttaaagataagttgttttgtgcatttattactaagcgtattgtgtataaagcagcttgtgttgtggatgttaatgatagtcattctatggctgttgttgatggtaaacaaattgatgatcatcgtatcactagtattactagtgataagtttgattttattattgggcatggtatgtcattttcaatgactacttttgaaattgcccaattgtatggttcttgtataacacctaatgtgtgttttgttaaaggtgatataattaaagtatctaagcttgttaaagcagaagttgttgtaaaccctgctaatggccatatggcacatggtggtggtgttgcaaaagctattgcagtagcagctggacagcagtttgttaaagagactaccgatatggttaagtctaaaggagtttgtgctactggagattgttatgtactacagggggcaaattatgtaaaactgtgcttaatgttgttggacctgatgcgagaacacagggtaaacaaagttatgtattgttagagcgtgtttataaacatcttaacaactatgactgtgttgttacaactttgatctcagctggtatatttagtgtgccttctgatgtgtctttaacatatctacttggtactgctaagaaacaagttgttcttgttagcaataatcaagaggattttgatcttatttctaagtgtcagataactgctgttgagggcactaagaaattggcagcgcgtctttatttaatgttggacgttccattgtttacgaaacagatgctaataagttgattttaatcaatgacgttgcatttgtttcgacatttaatgttttacaggatgttttatccttaagacatgatatagcacttgatgatgatgcacgaaccttcgttcagagcaatgttgatgttgtacctgagggttggcgtgttgtcaataagttttatcaaattaatggtgttagaaccgttaagtattttgagtgtactggaggcatagatatatgcagccaggataaagtttttggttatgtacagcagggtatttttaataaggctactgttgctcaaattaaagccttgtttttggataaagtggacatcttgctaactgttgatggtgttaatttcactaataggtttgtgcctgttggtg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TABLE 4 Biological Assay Results for Assessed siNA SARS-CoV-2 nanolucpSiCHECK-2 reporter pSiCHECK-2 reporter assay Cos-7 at hACE-2 A549 assayassay Cos-7 least 50% inhibition A: <0.1 nM EC50; A: <0.2 nM EC50; yes(y)/no (n)/undetermimed (u). B: 0.1-1.0 nM EC50; B: 0.2-1.0 nM EC50;siRNAs w/>70% inhib. were followed siNA Name C: >1 nM EC50 C: >1 nM EC50up w/EC50 (hACE-2 A549 assay) ds-siNA-006 n ds-siNA-007 n ds-siNA-008 nds-siNA-009 n ds-siNA-010 u ds-siNA-011 B y ds-siNA-012 y ds-siNA-013 nds-siNA-014 n ds-siNA-015 n ds-siNA-016 n ds-siNA-017 n ds-siNA-018 B yds-siNA-019 y ds-siNA-020 y ds-siNA-021 y ds-siNA-022 n ds-siNA-023 nds-siNA-024 n ds-siNA-025 u ds-siNA-026 u ds-siNA-027 y ds-siNA-028 nds-siNA-029 n ds-siNA-030 B y ds-siNA-031 n ds-siNA-032 n ds-siNA-033 uds-siNA-034 u ds-siNA-035 n ds-siNA-036 y ds-siNA-037 n ds-siNA-038 nds-siNA-039 A y ds-siNA-040 A y ds-siNA-041 y ds-siNA-042 n ds-siNA-043n ds-siNA-044 n ds-siNA-045 n ds-siNA-046 y ds-siNA-047 y ds-siNA-048 yds-siNA-049 n ds-siNA-050 n ds-siNA-051 B y ds-siNA-052 y ds-siNA-053 nds-siNA-054 n ds-siNA-055 n ds-siNA-056 n ds-siNA-057 u ds-siNA-058 uds-siNA-059 u ds-siNA-060 y ds-siNA-061 B y ds-siNA-062 B y ds-siNA-063n ds-siNA-064 y ds-siNA-065 y ds-siNA-066 n ds-siNA-067 B y ds-siNA-068n ds-siNA-069 n ds-siNA-070 n ds-siNA-071 n ds-siNA-072 n ds-siNA-073 nds-siNA-074 n ds-siNA-075 C y ds-siNA-076 y ds-siNA-077 n ds-siNA-078 nds-siNA-079 u ds-siNA-080 n ds-siNA-081 A y ds-siNA-082 B y ds-siNA-083B y ds-siNA-084 y ds-siNA-085 y ds-siNA-086 n ds-siNA-087 A yds-siNA-088 y ds-siNA-089 B y ds-siNA-090 n ds-siNA-091 n ds-siNA-092 nds-siNA-093 n ds-siNA-094 n ds-siNA-095 B B y ds-siNA-096 y ds-siNA-097n ds-siNA-098 y ds-siNA-099 n ds-siNA-100 n ds-siNA-101 n ds-siNA-102 nds-siNA-103 n ds-siNA-104 n ds-siNA-105 u ds-siNA-106 B y ds-siNA-107 yds-siNA-108 y ds-siNA-109 n ds-siNA-110 n ds-siNA-111 n ds-siNA-112 nds-siNA-113 y ds-siNA-114 y ds-siNA-115 B y ds-siNA-116 y ds-siNA-117 nds-siNA-118 n ds-siNA-119 y ds-siNA-120 u ds-siNA-121 u ds-siNA-122 yds-siNA-123 n ds-siNA-124 n ds-siNA-125 B y ds-siNA-126 n ds-siNA-127 nds-siNA-128 u ds-siNA-129 u ds-siNA-130 n ds-siNA-131 y ds-siNA-132 nds-siNA-133 n ds-siNA-134 A y ds-siNA-135 A y ds-siNA-136 y ds-siNA-137n ds-siNA-138 n ds-siNA-139 n ds-siNA-140 n ds-siNA-141 n ds-siNA-142 yds-siNA-143 y ds-siNA-144 n ds-siNA-145 n ds-siNA-146 B y ds-siNA-147 nds-siNA-148 n ds-siNA-149 n ds-siNA-150 C y ds-siNA-151 n ds-siNA-152 uds-siNA-153 u ds-siNA-154 u ds-siNA-155 y ds-siNA-156 B y ds-siNA-157 By ds-siNA-158 n ds-siNA-159 y ds-siNA-160 y ds-siNA-161 n ds-siNA-162 By ds-siNA-163 n ds-siNA-164 y ds-siNA-165 y ds-siNA-166 y ds-siNA-167 yds-siNA-168 n ds-siNA-169 n ds-siNA-170 C B y ds-siNA-171 y ds-siNA-172y ds-siNA-173 B y ds-siNA-174 u ds-siNA-175 y ds-siNA-176 C A yds-siNA-177 A y ds-siNA-178 B y ds-siNA-179 B y ds-siNA-180 B yds-siNA-181 y ds-siNA-182 y ds-siNA-183 A y ds-siNA-184 B y ds-siNA-185n ds-siNA-186 n ds-siNA-187 n ds-siNA-188 n ds-siNA-189 n ds-siNA-190 yds-siNA-191 y ds-siNA-192 y ds-siNA-193 B B y ds-siNA-194 n ds-siNA-195n ds-siNA-196 A B ds-siNA-197 B B ds-siNA-198 B A ds-siNA-199 A Bds-siNA-217 A ds-siNA-218 A ds-siNA-219 A ds-siNA-220 A ds-siNA-221 Ads-siNA-222 A

1. A short interfering nucleic acid (siNA) molecule comprising: (a) asense strand comprising a first nucleotide sequence, wherein the firstnucleotide sequence is 15 to 30 nucleotides in length and comprises anucleotide sequence that is at least about 60%, 65%, 70%, 75%, 80%, 85%,90%, 95%, or 100% identical to an RNA corresponding to of any one of SEQID NOs: 1-1203 and 2411-3392; and (b) an antisense strand comprising asecond nucleotide sequence, wherein the second nucleotide sequence is 15to 30 nucleotides in length and comprises a nucleotide sequence that isat least about 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, or 100%complementary to the first nucleotide sequence.
 2. The siNA molecule ofclaim 1, wherein the first nucleotide sequence is identical to an RNAcorresponding to 15 to 30 nucleotides within positions 190-216, 233-279,288-324, 455-477, 626-651, 704-723, 3352-3378, 5384-5403, 6406-6483,7532-7551, 9588-9606, 10484-10509, 11609-11630, 11834-11853,12023-12045, 12212-12234, 12401-12420, 12839-12867, 12885-12924,12966-12990, 13151-13176, 13363-13386, 13388-13416, 13458-13416,13458-13520, 13762-13790, 14290-14312, 14404-14429, 14500-14531,14623-14642, 14650-14687, 14698-14717, 14722-14748, 14750-14777,14821-14846, 14854-14873, 14875-14903, 14962-14990, 14992-15020,15055-15140, 15172-15200, 15310-15332, 15346-15367, 15496-15518,15622-15644, 15838-15869, 15886-15905, 15985-16010, 16057-16079,16186-16205, 16430-16448, 16822-16865, 16954-16976, 17008-17042,17080-17111, 17137-17156, 17269-17289, 17530-17549, 17563-17582,17680-17699, 17746-17765, 17857-17876, 17956-17975, 18100-18122,18196-18218, 19618-19639, 19783-19802, 19831-19850, 20107-20130,20776-20795, 21502-21524, 24302-24325, 24446-24465, 24620-24651,24662-24684, 25034-25057, 25104-25128, 25364-25387, 25502-25530,26191-26227, 26232-26267, 26269-26330, 26332-26394, 26450-26481,26574-26600, 27003-27064, 27093-27111, 27183-27212, 27382-27407,27511-27533, 27771-27818, 28270-28296, 28397-28434, 28513-28546,28673-28692, 28706-28726, 28744-28794, 28799-28827, 28946-28972,28976-29034, 29144-29172, 29174-29196, 29228-29259, 29285-29305,29342-29394, 29444-29463, 29543-29566, 29598-29630, 29652-29687,29689-29731, 29733-29757.
 3. The siNA molecule of claim 1, wherein thesecond nucleotide sequence is complementary to an RNA corresponding to15 to 30 nucleotides within positions 190-216, 233-279, 288-324,455-477, 626-651, 704-723, 3352-3378, 5384-5403, 6406-6483, 7532-7551,9588-9606, 10484-10509, 11609-11630, 11834-11853, 12023-12045,12212-12234, 12401-12420, 12839-12867, 12885-12924, 12966-12990,13151-13176, 13363-13386, 13388-13416, 13458-13416, 13458-13520,13762-13790, 14290-14312, 14404-14429, 14500-14531, 14623-14642,14650-14687, 14698-14717, 14722-14748, 14750-14777, 14821-14846,14854-14873, 14875-14903, 14962-14990, 14992-15020, 15055-15140,15172-15200, 15310-15332, 15346-15367, 15496-15518, 15622-15644,15838-15869, 15886-15905, 15985-16010, 16057-16079, 16186-16205,16430-16448, 16822-16865, 16954-16976, 17008-17042, 17080-17111,17137-17156, 17269-17289, 17530-17549, 17563-17582, 17680-17699,17746-17765, 17857-17876, 17956-17975, 18100-18122, 18196-18218,19618-19639, 19783-19802, 19831-19850, 20107-20130, 20776-20795,21502-21524, 24302-24325, 24446-24465, 24620-24651, 24662-24684,25034-25057, 25104-25128, 25364-25387, 25502-25530, 26191-26227,26232-26267, 26269-26330, 26332-26394, 26450-26481, 26574-26600,27003-27064, 27093-27111, 27183-27212, 27382-27407, 27511-27533,27771-27818, 28270-28296, 28397-28434, 28513-28546, 28673-28692,28706-28726, 28744-28794, 28799-28827, 28946-28972, 28976-29034,29144-29172, 29174-29196, 29228-29259, 29285-29305, 29342-29394,29444-29463, 29543-29566, 29598-29630, 29652-29687, 29689-29731,29733-29757, or 29770-29828 of SEQ ID NO:
 2407. 4. The siNA molecule ofclaim 1, wherein the sense strand comprises a nucleotide sequenceidentical to an RNA corresponding to any one of SEQ ID NOs: 1-1203 and2411-3392.
 5. The siNA molecule of claim 1, wherein the antisense strandcomprises a nucleotide sequence identical to an RNA corresponding to anyone of SEQ ID NOs: 1204-2406 and 3393-4374 and (b) a sense strand. 6.The siNA of claim 1, wherein the sense strand comprises 15 or moremodified nucleotides independently selected from a 2′-O-methylnucleotide and a 2′-fluoro nucleotide, wherein at least one modifiednucleotide is a 2′-O-methyl nucleotide and the nucleotide at position 3,5, 7, 8, 9, 10, 11, 12, 14, 17, and/or 19 from the 5′ end is a 2′-fluoronucleotide; and the antisense strand comprises 15 or more modifiednucleotides independently selected from a 2′-O-methyl nucleotide and a2′-fluoro nucleotide, wherein at least one modified nucleotide is a2′-O-methyl nucleotide and at least one modified nucleotide is a2′-fluoro nucleotide.
 7. The siNA of claim 1, wherein the sense strandcomprises 15 or more modified nucleotides independently selected from a2′-O-methyl nucleotide and a 2′-fluoro nucleotide, wherein at least onemodified nucleotide is a 2′-O-methyl nucleotide and at least onemodified nucleotide is a 2′-fluoro nucleotide; and the antisense strandcomprises 15 or more modified nucleotides independently selected from a2′-O-methyl nucleotide and a 2′-fluoro nucleotide, wherein at least onemodified nucleotide is a 2′-O-methyl nucleotide and the nucleotide atposition 2, 5, 6, 8, 10, 14, 16, 17, and/or 18 from the 5′ end is a2′-fluoro nucleotide.
 8. The siNA of claim 1, wherein the sense strandcomprises 16, 17, 18, 19, 20, 21, 22, 23, or more modified nucleotidesindependently selected from a 2′-O-methyl nucleotide and a 2′-fluoronucleotide.
 9. The siNA of claim 1, wherein 70%, 75%, 80%, 85%, 90%, 95%or 100% of the nucleotides in the sense strand are modified nucleotidesindependently selected from a 2′-O-methyl nucleotide and a 2′-fluoronucleotide.
 10. The siNA of claim 1, wherein: (i) at least 2, 3, 4, 5,or 6 modified nucleotides of the sense strand are 2′-fluoro nucleotides;(ii) no more than 10, 9, 8, 7, 6, 5, 4, 3, or 2 modified nucleotides ofthe sense strand are 2′-fluoro nucleotides; (iii) at least 10, 11, 12,13, 14, 15, 16, 17, 18, 19, 20, 21, or 22 modified nucleotides of thesense strand sequence are 2′-O-methyl nucleotides; and/or (iv) no morethan 25, 24, 23, 22, 21, 20, 19, 18, 17, 16, 15, 14, 13, 12, 11, 10, 9,8, 7, 6, 5, 4, 3, or 2 modified nucleotides of the sense strand are2′-O-methyl nucleotides.
 11. The siRNA of claim 1, wherein the antisensestrand comprises 16, 17, 18, 19, 20, 21, 22, 23, or more modifiednucleotides independently selected from a 2′-O-methyl nucleotide and a2′-fluoro nucleotide.
 12. The siNA of claim 1, wherein 70%, 75%, 80%,85%, 90%, 95% or 100% of the nucleotides in the antisense strand aremodified nucleotides independently selected from a 2′-O-methylnucleotide and a 2′-fluoro nucleotide.
 13. The siNA of claim 1, wherein:(i) at least 2, 3, 4, 5, or 6 modified nucleotides of the antisensestrand are 2′-fluoro nucleotides; (ii) no more than 10, 9, 8, 7, 6, 5,4, 3, or 2 modified nucleotides of the antisense strand are 2′-fluoronucleotides; (iii) at least 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20,21, or 22 modified nucleotides of the antisense strand sequence are2′-O-methyl nucleotides; and/or (iv) no more than 25, 24, 23, 22, 21,20, 19, 18, 17, 16, 15, 14, 13, 12, 11, 10, 9, 8, 7, 6, 5, 4, 3, or 2modified nucleotides of the antisense strand are 2′-O-methylnucleotides.
 14. The siNA of claim 1, wherein the sense strand and/orthe antisense strand comprise one or more phosphorothioateinternucleoside linkage(s).
 15. The siNA of claim 1, wherein the siNAfurther comprises a phosphorylation blocker and/or a 5′-stabilized endcap.
 16. The siNA of claim 1, wherein the sense strand further comprisesa TT sequence adjacent to the first nucleotide sequence.
 17. The siNA ofclaim 1, wherein at least one end of the siNA is a blunt end.
 18. ThesiNA of claim 1, wherein at least one end of the siNA comprises anoverhang, wherein the overhang comprises at least one nucleotide. 19.The siNA of claim 1, wherein at both ends of the siNA comprise anoverhang, wherein the overhang comprises at least one nucleotide. 20.The siNA of claim 1, wherein the sense strand and/or the antisensestrand comprises one or more modified nucleotides.
 21. The siNA of claim1, wherein the sense strand and/or the antisense strand furthercomprises at least 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15 ormore phosphorothioate internucleotide linkages. 22-23. (canceled) 24.The siNA of claim 20, wherein the modified nucleotides are independentlyselected from 2′-O-methyl nucleotides and 2′-fluoro nucleotides.
 25. ThesiNA of claim 0, wherein at least one 2′-fluoro nucleotide or2′-O-methyl nucleotide is a 2′-fluoro or 2′-O-methyl nucleotide mimic ofFormula (V):

wherein R¹ is a nucleobase, aryl, heteroaryl, or H, Q¹ and Q² areindependently S or O, R⁵ is —OCD₃, —F, or —OCH₃, and R⁶ and R⁷ areindependently H or D; or a 2′-fluoro nucleotide 2′-fluoro nucleotidemimic selected from


26. The siNA of claim 1, wherein the sense strand and/or antisensestrand comprises at least one modified nucleotide selected from

where R is H or alkyl (or AmNA(N-Me)) when R is alkyl);

wherein B is a nucleobase.
 27. The siNA of claim 1, wherein the ds-siNAfurther comprises a phosphorylation blocker and/or a 5′-stabilized endcap.
 28. The siNA of claim 0, wherein the phosphorylation blocker hasthe structure of Formula (IV):

wherein R¹ is a nucleobase, R⁴ is —O—R³⁰ or —NR³¹R³², R³⁰ is C₁-C₈substituted or unsubstituted alkyl; and R³¹ and R³² together with thenitrogen to which they are attached form a substituted or unsubstitutedheterocyclic ring.
 29. The siNA of claim 0, wherein R⁴ is —OCH₃ or—N(CH₂CH₂)₂O.
 30. The siNA of claim 26, wherein the phosphorylationblocker is attached to the 5′ end of the sense strand.
 31. The siNA ofclaim 0, wherein the phosphorylation blocker is attached to the 5′ endof the sense strand via one or more linkers independently selected froma phosphodiester linker, phosphorothioate linker, and phosphorodithioatelinker.
 32. The siNA of claim 0, wherein the 5′-stabilized end cap is a5′ vinylphosphonate.
 33. The siNA of claim 32, wherein the 5′vinylphosphonate is selected from a 5′-(E)-vinyl phosphonate or5′-(Z)-vinyl phosphonate.
 34. The siNA of claim 32, wherein the5′-vinylphosphonate is a deuterated vinyl phosphonate.
 35. The siNA ofclaim 34, wherein the deuterated vinylphosphonate is a mono-deuteratedvinylphosphonate or a di-deuterated vinylphosphonate.
 36. The siNA ofclaim 0, wherein the 5′-stabilized end cap has the structure of Formula(Ia):

wherein R¹ is a nucleobase, aryl, heteroaryl, or H, R² is

 —CH═CD-Z, —CD=CH—Z, —CD=CD-Z, —(CR²¹R²²)_(n)—Z, or —(C₂-C₆alkenylene)-Z and R²⁰ is hydrogen; or R² and R²⁰ together form a 3- to7-membered carbocyclic ring substituted with —(CR²¹R²²)_(n)—Z or —(C₂-C₆alkenylene)-Z; n is 1, 2, 3, or 4; Z is —ONR²³R²⁴,—OP(O)OH(CH₂)_(m)CO₂R²³, —OP(S)OH(CH₂)_(m)CO₂R²³, —P(O)(OH)₂,—P(O)(OH)(OCH₃), —P(O)(OH)(OCD₃), —SO₂(CH₂)_(m)P(O)(OH)₂, —SO₂NR²³R²⁵,—NR²³R²⁴, or —NR²³SO₂R²⁵; R²¹ and R²² either are independently hydrogenor C₁-C₆ alkyl, or R²¹ and R²² together form an oxo group; R²³ ishydrogen or C₁-C₆ alkyl; R²⁴ is —SO₂R²⁵ or —C(O)R²⁵; or R²³ and R²⁴together with the nitrogen to which they are attached form a substitutedor unsubstituted heterocyclic ring; R²⁵ is C₁-C₆ alkyl; and m is 1, 2,3, or
 4. 37. The siNA of claim 0, wherein R¹ is an aryl.
 38. The siNA ofclaim 0, wherein the aryl is a phenyl.
 39. The siNA of claim 26, whereinthe 5′-stabilized end cap has the structure of Formula (Ib):

wherein R¹ is a nucleobase, aryl, heteroaryl, or H, R² is

 —CH═CD-Z, —CD=CH—Z, —CD=CD-Z, —(CR²¹R²²)_(n)—Z, or —(C₂-C₆alkenylene)-Z and R²⁰ is hydrogen; or R² and R²⁰ together form a 3- to7-membered carbocyclic ring substituted with —(CR²¹R²²)_(n)—Z or —(C₂-C₆alkenylene)-Z; n is 1, 2, 3, or 4; Z is —ONR²³R²⁴,—OP(O)OH(CH₂)_(m)CO₂R²³, —OP(S)OH(CH₂)_(m)CO₂R²³, —P(O)(OH)₂,—P(O)(OH)(OCH₃), —P(O)(OH)(OCD₃), —SO₂(CH₂)_(m)P(O)(OH)₂, —SO₂NR²³R²⁵,—NR²³R²⁴, R²¹ and R²² are independently hydrogen or C₁-C₆ alkyl; R²¹ andR²² together form an oxo group; R²³ is hydrogen or C₁-C₆ alkyl; R²⁴ is—SO₂R²⁵ or —C(O)R²⁵; or R²³ and R²⁴ together with the nitrogen to whichthey are attached form a substituted or unsubstituted heterocyclic ring;R²⁵ is C₁-C₆ alkyl; and m is 1, 2, 3, or
 4. 40. The siNA of claim 26,wherein the 5′-stabilized end cap is selected from the group consistingof Formula (1) to Formula (15), Formula (9X) to Formula (12X), andFormula (9Y) to Formula (12Y):

wherein R¹ is a nucleobase, aryl, heteroaryl, or H.
 41. The siNA ofclaim 26, wherein the 5′-stabilized end cap is selected from the groupconsisting of Formulas (1A)-(15A), Formulas (9B)-(12B), Formulas(9AX)-(12AX), Formulas (9AY)-(12AY), Formulas (9BX)-(12BX), and Formulas(9BY)-(12BY):


42. The siNA of any of claim 26, wherein the 5′-stabilized end cap isattached to the 5′ end of the antisense strand.
 43. The siNA of claim42, wherein the 5′-stabilized end cap is attached to the 5′ end of theantisense strand via one or more linkers independently selected from aphosphodiester linker, phosphorothioate linker, phosphoramidite (HEG)linker, triethylene glycol (TEG) linker, or phosphorodithioate linker.44. The siNA molecule of claim 1, wherein the sense strand consists of21 nucleotides.
 45. The siNA molecule of claim 44, wherein 2′-O-methylnucleotides are at positions 18-21 from the 5′ end of the sense strand.46. The siNA molecule of claim 1, wherein the antisense strand consistsof 23 nucleotides.
 47. The siNA molecule of claim 46, wherein2′-O-methyl nucleotides are at positions 18-23 from the 5′ end of theantisense strand.
 48. An siNA selected from ds-siNA-005; ds-siNA-006;ds-siNA-007; ds-siNA-008; ds-siNA-009; ds-siNA-010; ds-siNA-011;ds-siNA-012; ds-siNA-013; ds-siNA-014; ds-siNA-015; ds-siNA-016;ds-siNA-017; ds-siNA-018; ds-siNA-019; ds-siNA-020; ds-siNA-021;ds-siNA-022; ds-siNA-023; ds-siNA-024; ds-siNA-025; ds-siNA-026;ds-siNA-027; ds-siNA-028; ds-siNA-029; ds-siNA-030; ds-siNA-031;ds-siNA-032; ds-siNA-033; ds-siNA-034; ds-siNA-035; ds-siNA-036;ds-siNA-037; ds-siNA-038; ds-siNA-039; ds-siNA-040; ds-siNA-041;ds-siNA-042; ds-siNA-043; ds-siNA-044; ds-siNA-045; ds-siNA-046;ds-siNA-047; ds-siNA-048; ds-siNA-049; ds-siNA-050; ds-siNA-051;ds-siNA-052; ds-siNA-053; ds-siNA-054; ds-siNA-055; ds-siNA-056;ds-siNA-057; ds-siNA-058; ds-siNA-059; ds-siNA-060; ds-siNA-061;ds-siNA-062; ds-siNA-063; ds-siNA-064; ds-siNA-065; ds-siNA-066;ds-siNA-067; ds-siNA-068; ds-siNA-069; ds-siNA-070; ds-siNA-071;ds-siNA-072; ds-siNA-073; ds-siNA-074; ds-siNA-075; ds-siNA-076;ds-siNA-077; ds-siNA-078; ds-siNA-079; ds-siNA-080; ds-siNA-081;ds-siNA-082; ds-siNA-083; ds-siNA-084; ds-siNA-085; ds-siNA-086;ds-siNA-087; ds-siNA-088; ds-siNA-089; ds-siNA-090; ds-siNA-091;ds-siNA-092; ds-siNA-093; ds-siNA-094; ds-siNA-095; ds-siNA-096;ds-siNA-097; ds-siNA-098; ds-siNA-099; ds-siNA-100; ds-siNA-101;ds-siNA-102; ds-siNA-103; ds-siNA-104; ds-siNA-105; ds-siNA-106;ds-siNA-107; ds-siNA-108; ds-siNA-109; ds-siNA-110; ds-siNA-111;ds-siNA-112; ds-siNA-113; ds-siNA-114; ds-siNA-115; ds-siNA-116;ds-siNA-117; ds-siNA-118; ds-siNA-119; ds-siNA-120; ds-siNA-121;ds-siNA-122; ds-siNA-123; ds-siNA-124; ds-siNA-125; ds-siNA-126;ds-siNA-127; ds-siNA-128; ds-siNA-129; ds-siNA-130; ds-siNA-131;ds-siNA-132; ds-siNA-133; ds-siNA-134; ds-siNA-135; ds-siNA-136;ds-siNA-137; ds-siNA-138; ds-siNA-139; ds-siNA-140; ds-siNA-141;ds-siNA-142; ds-siNA-143; ds-siNA-144; ds-siNA-145; ds-siNA-146;ds-siNA-147; ds-siNA-148; ds-siNA-149; ds-siNA-150; ds-siNA-151;ds-siNA-152; ds-siNA-153; ds-siNA-154; ds-siNA-155; ds-siNA-156;ds-siNA-157; ds-siNA-158; ds-siNA-159; ds-siNA-160; ds-siNA-161;ds-siNA-162; ds-siNA-163; ds-siNA-164; ds-siNA-165; ds-siNA-166;ds-siNA-167; ds-siNA-168; ds-siNA-169; ds-siNA-170; ds-siNA-171;ds-siNA-172; ds-siNA-173; ds-siNA-174; ds-siNA-175; ds-siNA-176;ds-siNA-177; ds-siNA-178; ds-siNA-179; ds-siNA-180; ds-siNA-181;ds-siNA-182; ds-siNA-183; ds-siNA-184; ds-siNA-185; ds-siNA-186;ds-siNA-187; ds-siNA-188; ds-siNA-189; ds-siNA-190; ds-siNA-191;ds-siNA-192; ds-siNA-193; ds-siNA-194; ds-siNA-195; ds-siNA-196;ds-siNA-197; ds-siNA-198; ds-siNA-199; ds-siNA-200; ds-siNA-201;ds-siNA-202; ds-siNA-203; ds-siNA-204; ds-siNA-205; ds-siNA-206;ds-siNA-207; ds-siNA-208; ds-siNA-209; ds-siNA-210; ds-siNA-211;ds-siNA-212; ds-siNA-213; ds-siNA-214; ds-siNA-215; ds-siNA-216;ds-siNA-217; ds-siNA-218; ds-siNA-219; ds-siNA-220; ds-siNA-221; andds-siNA-222.
 49. The siNA of claim 48, wherein the siNA is selected fromds-siNA-196 (sense and antisense respectively comprising SEQ ID NOs:4578 and 4800), ds-siNA-197 (sense and antisense respectively comprisingSEQ ID NOs: 4579 and 4801), ds-siNA-198 (sense and antisenserespectively comprising SEQ ID NOs: 4580 and 4802), ds-siNA-199 (senseand antisense respectively comprising SEQ ID NOs: 4581 and 4803),ds-siNA-217 (sense and antisense respectively comprising SEQ ID NOs:4599 and 4821), ds-siNA-218 (sense and antisense respectively comprisingSEQ ID NOs: 4600 and 4822), ds-siNA-219 (sense and antisenserespectively comprising SEQ ID NOs: 4601 and 4823), ds-siNA-220 (senseand antisense respectively comprising SEQ ID NOs: 4602 and 4824),ds-siNA-221 (sense and antisense respectively comprising SEQ ID NOs:4603 and 4825), and ds-siNA-222 (sense and antisense respectivelycomprising SEQ ID NOs: 4604 and 4826).
 50. The siNA of claim 48, whereinthe siNA is selected from ds-siNA-196 (sense and antisense respectivelycomprising SEQ ID NOs: 4578 and 4800), ds-siNA-197 (sense and antisenserespectively comprising SEQ ID NOs: 4579 and 4801), ds-siNA-198 (senseand antisense respectively comprising SEQ ID NOs: 4580 and 4802), andds-siNA-199 (sense and antisense respectively comprising SEQ ID NOs:4581 and 4803).
 51. The siNA of claim 48, wherein the siNA is selectedfrom, ds-siNA-217 (sense and antisense respectively comprising SEQ IDNOs: 4599 and 4821), ds-siNA-218 (sense and antisense respectivelycomprising SEQ ID NOs: 4600 and 4822), ds-siNA-219 (sense and antisenserespectively comprising SEQ ID NOs: 4601 and 4823), ds-siNA-220 (senseand antisense respectively comprising SEQ ID NOs: 4602 and 4824),ds-siNA-221 (sense and antisense respectively comprising SEQ ID NOs:4603 and 4825), and ds-siNA-222 (sense and antisense respectivelycomprising SEQ ID NOs: 4604 and 4826).
 52. A pharmaceutical compositioncomprising at least one siNA according to claim 1 and a pharmaceuticallyacceptable carrier or diluent.
 53. A pharmaceutical compositioncomprising at least one siNA according to claim 48 and apharmaceutically acceptable carrier or diluent. 54-55. (canceled)
 56. Amethod of treating a disease caused by a β-coronavirus in a subject inneed thereof, comprising administering the subject at least one siNAaccording to claim
 1. 57-75. (canceled)
 76. A method of treating aβ-coronavirus-caused disease in a subject in need thereof, comprisingadministering the subject at least one siNA of claim
 48. 77-83.(canceled)